The book begins and ends at a pool of the Salinas River. This is a setting that is almost idyllic for George and particularly Lennie because it is away from any type of society. It is ideal for Lennie because in a place such as this, he is less of a danger to others. Since he does not really fit in with society (at least with the life on a ranch), he is safer in nature, away from others. Steinbeck emphasizes the safety and tranquility of this spot in the opening lines:
The water is warm too, for it has slipped twinkling over the yellow sands in the sunlight before reaching the narrow pool. On one side of the river the golden foothill slopes curve up to the strong and rocky Gabilan Mountains, but on the valley side the water is lined with trees--willows fresh and green with every spring, carrying in their lower leaf junctures the debris of winter's flooding;
Notice the adjectives that describe the setting: warm, twinkling, golden, strong, fresh. This is a refuge for Lennie and George if Lennie gets into trouble. In this first chapter, the landscape is strong, fresh, full of life and hope.
Lennie has gotten into trouble before, so there is the idea that he and George have had to retreat to some refuge before. Lennie makes some mistake, he and George seek refuge, and then they make a new plan for some new destination. Only, this time in Chapter Six, George decides the cycle can not continue. So, there are similarities in setting and in the repetition of the cycle, but the obvious difference is that George feels compelled to end this cycle because he can no longer allow Lennie to (unintentionally) hurt others. In the last chapter, Lennie is more tentative whereas in the first chapter he plods along like a wild animal. The mood in Chapter Six is more tense and foreboding. There is also a foreshadowing moment of Lennie's death with the image of one animal killing another:
A water snake glided smoothly up the pool, twisting its periscope head from side to side; and it swam the length of the pool and came to the legs of a motionless heron that stood in the shallows. A silent head and beak lanced down and plucked it out by the head, and the beak swallowed the little snake while its tail waved frantically.
Some of the adjectives describing the landscape are different than those used in the first chapter. There are "brown, dry leaves" on the ground and gusts of wind. And the heron waits for its next victim. This setting in Chapter Six is more tense and violent than the relatively calm and soothing landscape described in Chapter One. Steinbeck begins the book with a sense of hope: the hope of Lennie and George achieving their dream of owning a farm. The book ends with George accepting the impossibility of that dream.