The speaker of the poem is trying to convince a woman to have a sexual relationship with him. Donne uses a flea in his metaphor in an attempt to help his speaker persuade the woman.

First, the speaker is trying to make the point that a flea is literally tiny and insignificant. By comparing the flea to sex, he's creating the argument that sex is a small, insignificant act just as the flea is a small, insignificant creature.

Secondly, the speaker describes the flea as a blood-sucking creature. The flea, which has sucked the blood of each of them, now contains both their blood. With the mixing of their blood inside the flea, they, too, have become one. While this is a stretch, the selection of a flea becomes important. Donne needed to pick a comparison that would literally join the speaker and the woman together. Since fleas move from thing to thing sucking blood without care, the flea reinforces a casual sexual union. And since their blood mixing in this way cannot be considered "A sin, nor shame, nor loss of maidenhead," it reinforces again that sex is not a big deal because they have already come together within the flea. Therefore, sex will be as insignificant as a flea bite.

It seems Donne selects a flea because the literal characteristics of the flea (blood-sucking, tiny/significant) help reinforce the physical characteristics of sex that he so deeply desires from the woman. Using a flea helps strengthen his argument.