Pedroia was playing at Double-A Portland before suffering another setback. The 2008 AL MVP has played in only six games this season.
Knee injuries have bothered Pedroia since having a "cleanup" surgery after the 2017 season. He was limited to three games last season.
Boston had hoped Pedroia would return before the end of May. A timetable for his return to the minor leagues has not been announced.
Pedroia had four hits in 20 at-bats during his rehab stint. He played 24 innings at second base.
Rookie Michael Chavis has seen increased time at second base with Pedroia out. Chavis is hitting .282 with six home runs and 19 RBIs in 20 games.
Pedroia is under contract with the Red Sox through 2021. The four-time All-Star is a career .299 hitter and is only 195 hits shy of 2,000 career hits.