"Today I’m taking the necessary steps to form an exploratory committee to test the waters for the U.S. Senate," he said in a statement.
"We need to fix a broken Washington where progress is being hampered by partisan gridlock. If we continue to elect the same Washington politicians, we can not expect different results," he said.
Winslow's interest in the race comes as many of the first- and second-tier candidates have declined to run.
Brown, long considered the most viable contender for a special election in blue Massachusetts that looks tough by any metrics, announced he would not run on Friday, and a handful of other candidates dropped out in the following days.
Former Gov. Bill Weld, former House GOP contender Richard Tisei and former Lt. Gov. Kerry Healey all announced by Monday evening they weren't interested in a run.
"While I am grateful for and value the advice of those who have been urging me to run, I have decided not to be a candidate in the Massachusetts US Senate special election," Healey said in her statement.
That leaves the GOP with a shallow bench of relatively unknown state legislators, including Winslow, state Senate Minority leader Bruce Tarr and Assistant Senate Minority Leader Robert Hedlund, as well as Worcester Sheriff Lew Evangelidis and local businessman Gabriel Gomez.
However, the Massachusetts Republican Party feels it has a chance to win going into the election.
"The fact is the Democratic Party will field a mediocre congressman with a highly partisan record who has been part of the Washington gridlock. A Republican Senator from Massachusetts will offer the bipartisan leadership to solve our nation's problems," said Massachusetts GOP Chairwoman Kirsten Hughes.
Massachusetts Democratic Party Chairman John Walsh nationalized Winslow's candidacy in a statement that focused largely on his connections to former Mass. Gov. and GOP presidential nominee Mitt Romney.
Walsh charged in his statement that Winslow, who served as then-Gov. Mitt Romney's chief legal counsel from 2002-2004, is a member of "Romney's inner circle," and said he spent last year as one of Romney's "apologists and political attack dogs."
"Winslow will work just as hard to stop President Obama's agenda in the Senate as he did to deny him a second term and send Mitt Romney to the White House. During his time on Beacon Hill, Republican Winslow has shown that he is more interested in grabbing headlines than getting work done for the people of the Commonwealth," he said.
Any prospective candidates have until Feb. 27 to collect the necessary signatures to qualify for the ballot.
Democratic Reps. Stephen Lynch and Ed MarkeyEd MarkeyDems rip Trump administration for revoking Obama's transgender directive A guide to the committees: Senate GOP sets sights on internet privacy rules MORE are pursuing the Democratic nomination.
--This piece has been updated to reflect comment from the Massachusetts Democratic Party.