MSNBC says this ...
While the exactly reason Lott is stepping down before he finishes his term is unknown, the general speculation is that a quick departure immunizes Lott against tougher restrictions in a new lobbying law that takes effect at the end of the year. That law would require Senators to wait two-years before entering the lucrative world of lobbying Congress.
By resigning now, Sen. Lott can go right to lobbying in a year and make a few boatloads of money. Pure sleaze and greed. Oh, I'm sure he'll say something about "family" or some other pretty excuse, but it's really about money. The lobbying reform that takes effect next year makes corruption harder for members of congress, so Lott is racing to sell out under the wire.
Republican values have a price tag. Buy a Senator now while they're on sale.
Update: Just now on NPR, Cokie Roberts (who I almost never agree with) said "he's going to work as a lobbyist" and made it sound like that's a good thing.