Manny Machado slid into second base on a force play and appeared to spike Pedroia in the back of the left leg.
Machado, who said he did not intend to hurt Pedroia and texted him after the game to express that, attempted to break Pedroia's fall before the four-time AL All-Star crumpled to the ground. Pedroia gingerly got to his feet before being helped off the field. It was unclear whether Pedroia twisted the knee.
"Extremely late slide," Red Sox manager John Farrell said. "And the argument at the time was, if the rule is in place to protect the middle infielder, well, then it didn't work tonight.
Pedroia shrugged off mention of the slide rule.
"I don't even know what the rule is," Pedroia said. "I've turned the best double play in the major leagues for 11 years. I don't need the f---ing rule, let's be honest. The rule is irrelevant. The rule is for people with bad footwork, and that's it."
Pablo Sandoval moved from third base to second base to replace Pedroia.
Farrell said the rule says the second baseman must deliberately and willfully attempt a double play.
"When you're cleaned out beyond second base and the runner never held second base completely, to me, the rule failed tonight," Farrell said.
Asked if he thought the play was dirty, Farrell repeated, "It was a late slide."
Information from The Associated Press and ESPN's Scott Lauber was used in this report.