Background: Estrogen is a principal female sex hormone that originally characterized by its importance in sexual growth and reproduction. Nevertheless, emergent evidence proposes clinical relationship between estrogen/ estrogen receptors and gastric diseases. This association is definitely under several investigated topics. Aim: The current study designed to explore exogenous estrogen effect on indomethacin-induced gastric ulcers in postmenopausal female rats. Matrial and methods: Twenty-four female rats (200 ± 20 gram BW) were allocated randomly into four groups; control, ulcer-induced, ranitidine-treated and (ranitidine&estradiol velerate) combined-treated group. Animal in all group except control subjected to ovariectomy to assimilate menopausal condition. At end of the experiment, the stomach fundus examined macroscopically to assess the ulcer severity and ulcer score in different groups. Histopatholgical and biochemical evaluation also were performed and all results were statistically analyzed. Results: Indomethacin-induced gastric ulcer in ovariectomized rats showed destroyed fundic mucosa and mucus layer, increase oxidative stress markers, inflammatory mediators and myeloperoxidase. Treatment with ranitidine attenuated the histological and biochemical changes but within limits. Better improvement was accomplished when ranitidine combined with estrogen. Conclusion: The postmenopausal women should be supplemented with estrogen not only to control menopausal symptoms but also to protect and maintain gastric mucosal integrity.