"Rory, I accept your challenge," Penn posted late Tuesday night.
MacDonald (13-1) has won three consecutive fights since a loss to current UFC interim welterweight champion Carlos Condit. He submitted Che Mills earlier this year at UFC 145.
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The site said UFC 152 on September 22 from Toronto, Ontario, Canada would be the targeted date.
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Get more great MMA news and analysis over at Fightline.