Abstract: Alpha-2 adrenergic receptors have antiulcer activity. Omeprazole and famotidine are anti-ulcerative drugs. In this study the role of alpha-2 adrenergic receptors in the antiulcerative activity of famotidine and omeprazole was examined pharmacologically and biochemically. Anti-ulcerative effects of all drugs (famotidine, omeprazole, histamine and yohimbine) were investigated on indomethacin-induced gastric ulcer model in rats. At first, mentioned drugs were given to 24 h-fasted rats. Then, 25 mg kg-1 indomethacine was given to induce gastric ulcer. Six hours after the administration of indomethacin, the animals were euthanized with high-dose anesthetic. The stomachs of the animals were removed and the ulcerative focuses located on the surface of the stomach were macroscopically evaluated. Thereafter, all the stomachs were sent to the laboratory of biochemistry for the measurement of the levels of total glutathione, malondialdehyde and the activity of superoxide dismutase, myeloperoxidase. Mean area of ulcer was 31.6, 1.08 and 0.83 mm2 in the rats of the control, famotidine and omeprazole groups treated with indomethacin, respectively. It was 29.3 mm2 in the indomethacin control group and, respectively, 24.5 and 26.1 mm2 in the famotidine and omeprazole that received yohimbine groups. It was 30 mm2 in the indomethacin control group, in the famotidine and omeprazole + histamine group it was 0.91 and 0.16 mm2. In the histamine and yohimbine alone groups, ulcer was not observed. It was found that alpha-2 adrenergic receptors had a role in anti-ulcer mechanism of famotidine and omeprazole. Moreover, it was seen that there was a direct relation between alpha-2 adrenergic receptors and oxidant-antioxidant parameters.