Matsuzaka, who's been on Boston's disabled list since April 3 with a neck strain, walked one, struck out three and hit two batters.
He threw 43 of 73 pitches for strikes and reached 93 mph on McCoy Stadium's radar gun.
"I felt I had a good feel on the ball today," Matsuzaka said through an interpreter. "The best thing was I didn't experience any problems and I had good command of my fastball."
The only hits he allowed were a line-drive double by Jacques Jones in the third and a fly-ball double down the right-field line by Luke Hughes in the fourth.
Rochester loaded the bases with two outs in the fifth on a walk and two hit batters. Matsuzaka escaped this jam by retiring Matt Tolbert on a foul popup to third.
"This is the first time I was able to go through my normal routine going into a game," Matsuzaka said. "Until this point, I've been pitching in simulated games and pitching in relief. It was a little difficult to grasp my routine, but I think I was able to do that and go about business in a normal way today.
"My fastball was good, but my slider and changeup weren't that great. I think I really need those two pitches for me to put a better ballgame together."
Matsuzaka made two spring relief appearances for Boston before he was placed on the disabled list. Over a total of six innings, he allowed four hits and compiled a 3.00 ERA.
"[It] sounded like he did pretty well," said Red Sox manager Terry Francona. "He worked quick, which means he felt pretty good about himself. We've all seen when he's not feeling good, he's staying out there, kind of walking around. From everything I saw, not just from the line, but from the report, it sounded like he was pretty good. It sounded like Alan Embree was a little bit better, too."
Matsuzaka felt the inning when Rochester loaded the bases wasn't bad because he became tired.
"It wasn't fatigue or anything like that," he said. "It was more of a technical issue. I think I was trying to be a little bit too fine with those pitches."
Matsuzaka was on an 80-85 pitch count and was surprised that he was removed before reaching that limit.
"I wasn't thinking about pitch count, but when I came in after the fourth inning, I was told I only had one more inning," he said. "At that point, I thought to myself maybe I'm getting up there in pitch count. But now that I heard what my pitch count was, I guess I could have gone out there for another inning."
Boston pitching coach John Farrell said near the end of Spring Training that he would like to see Matsuzaka be able to throw 95 pitches before he would pitch in a Major League game.
Matsuzaka expressed the opinion he could throw that many pitches now.
"I think even now, if it's just about throwing 95 pitches, I could do it now," he said. "Overall, I pitched better today than I thought I would be able to. I felt I was aggressive pitching in to left-handed batters. Overall, I had good feel for my pitches up high.
"I think after my next game is when I'll have a better idea of how many more (rehab) games I need to pitch."
So when will Matsuzaka return to the big leagues?
"I don't know that there's a plan that's etched in stone," said Francona. "I think we're more pleased with how he pitched today. That's the whole idea."
Mike Scandura is a contributor to MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.