Senator Harry Reid (NV) is not seeking re-election.
He told the New York Times that he had been contemplating retirement from the Senate for months.
Although the 75-year-old was badly hurt in an accident at his home gym, he said that mishap did not play a role in his decision.
Democrats lost majority control of the Senate in the last election, but he also denied that played a role.
"I understand this place," Reid said. "I have quite a bit of power as minority leader," he told the Times.
Reid's term ends at the end of 2016.