"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.
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.