Colon, the AL Cy Young award winner in 2005, started Wednesday night's game against the Kansas City Royals.
The Red Sox signed Colon to a minor league contract in spring training after he became a free agent following four seasons with the Angels. He was 21-8 with a 3.48 ERA in 2005, but injuries limited him to 29 games the past two seasons.
The right-hander was 6-8 with a 6.34 ERA last season in 19 games, 18 of them starts. He was on the disabled list from July 24 to Sept. 9 with irritation in his right elbow. In his last appearance in 2007, he had two strikeouts in a scoreless relief inning on Sept. 29 against Oakland.
In three rehab starts for Pawtucket, Colon was 2-0 with a 0.64 ERA.
Masterson was sent down after allowing one run in 6 1/3 innings of Tuesday night's 2-1 win over the Royals, his first major league decision. He had been recalled before the game because Boston needed a starter after playing a doubleheader Saturday.