The title Of Mice and Men has a lofty, epic quality which initially appears at odds with the humble people Steinbeck describes. It is based on the lines in "To a Mouse" by Robert Burns:

The best laid schemes o’ Mice an’ Men

Gang aft agley,

An’ lea’e us nought but grief an’ pain,

For promis’d joy!

Other educators have commented on the connection between the title of this book and the poem by Burns, but there is also some symbolic meaning behind the title.

Mice are not valued much in society. They are often seen as a nuisance, and mankind often seeks to destroy them. Lennie recognizes that mice aren't just an object of scorn and that they have redeeming qualities, too. He enjoys petting their soft fur and finds them a gentle source of comfort. Lennie appreciates mice as much as he appreciates other innocent creatures, such as rabbits and puppies.

Lennie is much like a mouse in this regard. He has an intellectual disability, and most of mankind doesn't value his existence. He is verbally insulted numerous times in the novel, and even George, who is his closest friend, makes comments like, "If I was a relative of yours I'd shoot myself." Because of his differences, Lennie stands outside the world of acceptance, much like the mice he cares for.

Of Mice and Men, then, comes to illustrate the symbolism of innocence versus evil in the novel. The innocent will find themselves persecuted by those who don't care to find value in their existence. After he accidentally kills Curley's wife, Lennie is killed by the one man he believed he could always count on. The title reflects the way those who are seen as weak are exploited by mankind.

Yes, y2kfain is right in making an explicit link between mice and men. Both in the play are shown to be immensely fragile and breakable. Lennie with his mice unfortunately foreshadows the failure at the centre of the play. Just as Lennie wants to pet the mice and keep them as pets, he accidentally and non-intentionally kills them. In the same way, George and Lennie desperately try to achieve their dream of "living of the fatta the land", but, despite their efforts, it ends in tragedy. In such a world our plans often come to naught.

The "Men" in the title of OF MICE and MEN refer to the common men who work on the ranch. For example, Slim, Candy, etc have simple desires and they are laborers. They want to obtain their own land so that they may work for themselves and obtain independence. The "Mice" in the title are an example of symbolism. Lennie loves mice, yet he pets them too hard and then they die. His fate in the book mirrors the fate of the mice he takes care of then kills accidently. Similiarly, George takes care of Lennie, yet he has to kill him intentionally. Both mice and men are fragile in regards to nature and the cruelties of humanity.

The significance of the title is in the futility of planning and the inevitablility of failure if the odds are stacked against you - as they are for George and Lennie. The novel is a condemnation of the American Dream, as has been said before but it also reflects on some of the principles of the American Constitution. All men are not created equal in the eyes of humanity, and characters like Lennie and George will always be judged by his weaknesses rather than his strengths.

The title Of Mice and Men is in reference to Robert Burns' poem.  The full phrase is "the best laid plans of mice and men often go awry."  I would look at the literal meaning of this quotation and apply it to the novel as a whole.

The title is from the Robert Burns poem, "To A Mouse, On Turning Up Her Nest."  The speaker observes a mouse whose carefully laid home is upturned by the cruel winter winds and bitter cold.  Despite all of the mouse's hard work, her efforts are for naught: "The best-laid schemes o' mice an 'men  / Gang aft agley," the poet writes (ie, often go awry.)

Likewise, Lennie and George's plans for a life of ease an "livin' off the fatta the lan'" also are forever disrupted by Lennie's accidental murder of Curley's wife.   Like the mouse, neither could have foreseen the drastic turn their lives would take, despite their plans for the future. 

The title Of Mice and Men was inspired by Robert Burns's 1795 poem "To a Mouse." After turning up a mouse's nest while plowing a field, Burns wrote:

The best laid schemes o’ Mice an’ Men

Gang aft agley,

An’ leave us nought but grief an’ pain,

For promis’d joy!

The poem itself mirrors the troubles that beset George and Lennie. First, there is the incident on which the poem is based. Burns had inadvertently destroyed the mouse's home, leaving it to flee to another place. George and Lennie are like the mouse, continually fleeing from trouble and poverty, vainly dreaming of permanence. Like the mouse in the poem, their schemes go wrong, despite all their dreaming and planning for the future. To the mouse, it must have seemed as though some inexplicable supernatural event suddenly tore it from its home. George and Lennie are similarly helpless, driven out of their shelter by circumstances and external forces outside their control, whether economic, social, or cosmic in nature.

The title of the poem yokes mice and men together to suggest that in the overall scheme of things, their fates are much the same. The same idea is expressed in Of Mice and Men: Lennie has no more control over his destiny than the dead mouse in his pocket or the one that was forced to run away from Burns's plow as its home was destroyed.

The title “Of Mice And Men comes from the Robert Burns poem “To a Mouse”. The most famous line is: The best laid schemes o' Mice an' Men, Gang aft agley, An' lea'e us nought but grief an' pain, For promis'd joy!” In the poem, Burns has disturbed the home of a field mouse with his plow. He is disturbed to see that the work the mouse has put into its home will be wasted. The line itself means that we can plan, but our plans often go wrong, leaving us with only grief and pain.

This relates very well to “Of Mice and Men.” In the story, Lennie and George have a dream. It’s a big dream for two people who have nothing. Each man places importance on the dream in a different way. For George, it is about finding a stable place to live so he no longer has to travel around, searching for work. Lennie, on the other hand, dreams of feeding rabbits. Lennie’s dream is a simple one, but it is important to him nonetheless. Lennie in the novel is the mouse. He is the one who leaves people alone unless they antagonize him. (example: Curley). At the end of the novel, George lives and Lennie dies, and this inevitable. The plan, so important for these two men, has gone wrong. George is left with grief and pain. As in the poem, when Burns tells the mouse that it is lucky it only looks forward and not back, George has to leave Lennie, his friend, behind. He is devastated but resolute at the end of the novel.

The title of the novel comes from an excerpt of a line from a poem written by poet Robert Burns in 1785 entitled "To a Mouse." It is said that Burns wrote the poem after accidentally destroying a mouse's nest. In the modern English translated version, the stanza containing the title states: 

But little Mouse, you are not alone,

In proving foresight may be vain:

The best laid schemes of mice and men

Go often askew,

And leave us nothing but grief and pain,

For promised joy!

So, in reading this stanza, you can see that the line essentially is saying that the best laid plans of mice and men rarely go as planned. Once you have read Of Mice and Men, you can probably see the connection with this line of the poem and general idea. George and Lennie have this amazing idea and have spent a significant amount of time planning it out. It seems as if nothing can go wrong -- and then it does.  Their plans are ruined and George is left alone with grief and pain. The title is essentially foreshadowing the end of the novel.