Abstract :Objective: The objective of the present study was to evaluate the effects of Rhodiola rosea in the indomethacin-induced ulcer model in rats and to clarify the underlying mechanisms of action. Methods: Rats in treatment groups were treated with Rhodiola rosea (RR) 14 days. Peptic ulcer was induced by indomethacin (IND) injection (100 mg/kg, p.o.). The groups (n = 6) were designed as; Group I (control); Group II (IND): After 24h of food starvation, rats were given only 100 mg/kg IND by oral gavage to induce gastric mucosal injury. Group III (ESO): Rats were pretreated with 20 mg/kg of ESO for 14 consecutive days by oral gavage. Group IV (RR): Rats were pretreated with 500 mg/kg RR for 14 consecutive days with oral gavage. Results: Rhodiola rosea effectively alleviated indomethacin-induced ulcer via reduction in oxidative stress (decreased MDA and increased SOD, and GSH). Moreover, Rhodiola rosea alleviated indomethacin-induced damage by regulating expressions of COX enzymes, prostaglandin E2, proliferating cell nuclear antigen (PCNA), cell proliferation, apoptosis and regulated the NF-κB signaling pathway. Rhodiola rosea also attenuated inflammatory injury by suppressing TNF- Keywords : Rhodiola rosea, indomethacin, oxidative stress, inflammation, peptic ulcer.