Lott resigned his leadership post in 2002 after an offhand remark during a social event. He said the United States would have been better off if Strom Thurmond, running as a segregationist, would have won the presidency in 1948.
Lott said he didn't plan to seek re-election in 2006 but Mississippi leaders have convinced him to change his mind, USA Today said.
The result has been a more outspoken Trent Lott. The Galveston County (Texas) Daily News reported on a Lott stop in which the senator rapped Frist and said Bush could hurt Republicans in the fall elections.
"You get out of Washington, you get relaxed, you let your hair down. And that's dangerous," Lott told USA Today.
There is speculation now, with Frist not seeking re-election but Lott doing so, that the Mississippi senator might try to regain his leadership spot.