The filmmaker wrote and directed the 2001 cult film that starred Jake Gyllenhaal, while he distanced himself from a direct-to-DVD sequel made by Chris Fisher.
A rumoured third instalment is apparently in the works, but Kelly said that he will definitely not be involved with the project.
He told MTV: "Absolutely not. I know nothing about it and I would never have any involvement with any existing or future sequel to Donnie Darko ever - ever! Never ever, ever, ever would I be involved with anything like that."
Kelly's next film project The Box, starring Cameron Diaz and Frank Langella, is due to open in autumn.