Radel pleaded guilty to cocaine possession in November and was sentenced to one-year probation.
A Radel spokesman confirmed his resignation to The Huffington Post on Monday.
In early January, Radel's spokesman said he would return to Congress six weeks after pleading guilty and checking into a rehab program. Many Republicans -- including the Republican Party of Florida and the state's governor, Rick Scott -- called on the congressman to step down after his arrest.
UPDATE -- 10:45 a.m. ET: In a letter, Radel wrote that his resignation is effective Monday at 6:30 pm.
"Regardless of some personal struggles in 2013, this year has already been tremendously positive as I focus on my health, family and faith," he said in a letter to House Speaker John Boehner. "Unfortunately, some of my struggles had serious consequences. While I have dealt with those issues on a personal level, it is my belief that professionally I cannot fully and effectively serve as a United States Representative to the place I love and call home, Southwest Florida."
Read Radel's letter below:
This story has been updated with more information on Radel and confirmation of his resignation.
Luke Johnson contributed to this report.