Bolelli broke the Australian Open champion at 2-2 and dominated much of the first set, but Nadal hit back in the second set, twice breaking the Italian and holding his nerve.
"He's a very good player,'' Nadal said. "He played big shots from the baseline. He improves every year. I want to congratulate him.''
Nadal will next face Bulgarian teenager Grigor Dimitrov.
Julien Benneteau of France upset third-seeded Nikolay Davydenko 6-3, 6-2, and Mikhail Youzhny of Russia eliminated sixth-seeded David Ferrer of Spain 6-2, 3-6, 6-2 to advance to the quarterfinals.
"The magic isn't back yet,'' said Youzhny, who won the event in 2007 but hadn't had a victory over a top-20 player since January 2008.
"I can do better,'' the Russian said. "Especially when things get tense, I play too cramped.''
Youzhny won on the strength of a clever backhand, keeping Ferrer off balance with sudden changes of speed and spin. The Spaniard was the first seeded player knocked out of the tournament at Rotterdam's Ahoy stadium.
Also Wednesday, seventh-seeded Jo-Wilfried Tsonga of France beat local favorite Jesse Huta Galung 7-6 (4) 7-6 (4), and defending champion Michael Llodra defeated Ivo Karlovic 4-6, 6-3, 6-4.
Karlovic served 25 aces and Llodra was plagued by double-faults in the first set.
Fourth-seeded Gilles Simon of France beat Philipp Kohlschreiber of Germany 7-5, 7-6 (1), and Mario Ancic of Croatia defeated Rainer Schuettler of Germany 7-5, 6-2.
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Youzhny upsets Ferrer in Rotterdam
Nadal rallies to win at ABN Amro