Rockhold is set to open as a -1,050 favorite. Bisping, who is stepping up on 17 days' notice, will open at +600.
The lines were set by Nick Kalikas of MMAOddsBreaker.com, with Rockhold in this fight being the biggest betting favorite Kalikas has opened in his career.
Rockhold (15-2) was originally supposed to defend his 185-pound title in a rematch against Chris Weidman, but the bout fell through this week when Weidman withdrew with a neck injury. Bisping (28-7), who is coming in on a three-fight win streak, will enter the first UFC title shot of his career.
UFC 199 will mark the second fight between the two. In the first meeting in November 2014, Rockhold hurt Bisping on the feet before finishing him via guillotine in the second round.
"The last time these two men fought, Luke Rockhold closed as a 5-to-1 betting favorite and he defeated Bisping convincingly," Kalikas said. "Most of the betting action was on Rockhold at the time. The stylistic matchup hasn't changed and now Bisping is on short notice.
"Rockhold should be able to have success on the feet and will have a huge advantage if the fight hits the canvas. I have a ton of respect for Bisping and he's on the best run of his career, but Rockhold is untouchable right now."
Fighting out of American Kickboxing Academy in San Jose, Rockhold is 5-1 since joining the UFC. He took the belt from Weidman in December in a fourth-round TKO win. He is also a former Strikeforce champion. Bisping is coming off one of the most significant wins of his career, a decision victory against Anderson Silva in February.