The Spaniard was leading 6-2 6-3 3-2 when Tipsarevic approached him during the changeover, shook his hand and announced he had to quit the match after one hour, 38 minutes.
The 23-year-old Tipsarevic, who reached the fourth round at Wimbledon, had his right side taped by a trainer early in the third set. An official later said the Serbian was troubled by a rib muscle injury he has had for five weeks.
There had been physical concern over French Open champion Nadal going into the match after the Spaniard had both knees wrapped and needed extra attention for his left knee during his first-round victory over Australian Alun Jones.
"I feel better today," said Nadal, who blasted in 28 winners against the Serb. "I feel a little more confidence in the knees.
"I'm not 100 percent yet. I run with a little bit of precaution, but so much better than the first day."
Nadal advanced to a third-round match against Jo-Wilfried Tsonga of France, a 7-6 2-6 7-5 6-4 winner against Briton Tim Henman.
"I hope I continue to improve for the next match against Tsonga. I played better, too," said Nadal, 21. "I feel more comfortable with the forehand and with the backhand, too."
Nadal said the 22-year-old Tsonga, ranked 74th, might be able to summon a big effort.
"I know he's a very aggressive player, a big server. Very good forehand. He plays with not much pressure, a little less than me," said Nadal. "He doesn't have much to lose. It's always easier to play like this."
