O'Donnell, long a fan of the gay-themed drama, called the show's producers to request a role on the show, the cable channel said Tuesday. Her first episode will air Sunday (10 p.m. ET).
The former talk-show host plays an abused woman who works at the local diner and falls for her mentor, played by Sharon Gless.
As one of the few TV programs to give gay issues the spotlight, "Queer as Folk" is clearly near to O'Donnell's heart. She and Kelli Carpenter O'Donnell, who were married in a civil ceremony Feb. 26 in San Francisco, are raising four children together and are strong advocates of gay marriage and adoption.
O'Donnell, 43, has been busy writing a blog and running a cruise business. She backs the R Family Vacations (search) cruise line, billed as the first to cater to gay and lesbian families.