The funnyman stars in the sitcom as an egocentric billionaire who tries to win back his high school sweetheart, played by Keri Russell.
Executives at America's Fox network have ordered 13 episodes of Running Wilde, but the future of the comedy is uncertain as viewing figures continue to decline.
Arnett is now backing a fan campaign to save the series from the axe, signing a petition to keep the show in production and asking others to do the same.
In a post on his Twitter.com page, he writes, "Never done a grassroots effort, but let's save the effing show Running Wilde forever! Or five decent seasons, plus a 6th for Two And A Half Men $$ (money)...
"Thanks to everyone who signed the petition... f**king ratings sucked... I guess America hates jokes?"