Announcing his candidacy in Boston, Brown, 50, a three-term member of the state Senate, touted himself as an anti-tax, anti-spending conservative who would take that philosophy to Washington, The Boston Globe reported.
He called the burgeoning national debt "just plain wrong" and said he could hold to his fiscally conservative beliefs because he isn't bound to special interests.
"Because I don't owe anybody anything, I'm free to tell the truth and fight for what's right for the people of Massachusetts," said Brown, a lawyer and officer in the National Guard.
Former White House chief of staff Andrew Card has decided not to run, leaving Brown and Canton Selectman Bob Burr the only declared Republican candidates. Former U.S. attorney Michael Sullivan has also been mentioned as a potential candidate.
On the Democratic side, state Attorney General Martha Coakley is running, while U.S. Reps. Stephen F. Lynch and Michael E. Capuano have said they plan to run, and Rep. John F. Tierney is considering jumping in.
Former Democratic congressman Joseph P. Kennedy II and Rep. Edward J. Markey have decided against entering the race.
Massachusetts has not elected a Republican to the U.S. Senate for nearly 40 years.