The 64-year-old Republican told a hometown crowd that he wants to continue working on federal issues related to Mississippi's recovery from Hurricane Katrina. He lost his own beachside house to Katrina on Aug. 29.
There had been speculation in political circles in Mississippi that Lott might retire, which could have set up a competitive race there in November,CBS News correspondent Bob Fuss reports. Lott's decision to seek a fourth term pretty much assures that Republicans will hold the seat.
The former Senate majority leader also has hinted that he might seek another leadership position in Washington. He lost his position in December 2002 after saying at Sen. Strom Thurmond's 100th birthday party that Mississippi had proudly voted for Thurmond when the South Carolinian ran for president as a segregationist in 1948.
Lott was first elected to the U.S. House in 1972 and to the Senate in 1988.
Lott said he had talked with family and friends before deciding to run.
"I've chosen Mississippi and America once again. I am going to ask the people of Mississippi to re-elect me," Lott said.
Lott has been in Washington for 37 years as a staff member, as a congressman and as a senator.
"But you know, I've enjoyed every minute of it," he had said earlier this month. "So I guess one thing I could say is, why end something that you're having so much fun at?"
Republicans hold 55 seats in the Senate, Democrats hold 44 and an independent who leans toward Democrats holds the other.
Party primaries are June 6. The general election is Nov. 7.
Lott was Senate majority leader from 1996 until June 2001, when Sen. James Jeffords of Vermont left the Republican Party to become an independent, tipping control of the Senate to the Democrats. Lott's title switched to minority leader, and after the GOP fared well in the 2002 elections he was slated to become majority leader again.
Lott said last month that he might seek another Senate leadership job if he wins another term. He has a news conference scheduled Wednesday in Washington to discuss that issue.
The current majority leader, Republican Bill Frist of Tennessee, already has announced that he's not seeking re-election this year.