Tricyclic antidepressants are particularly useful in the treatment of endogenous depression. Since the 1950s, tricyclic antidepressants (TCAs) have also been used for the treatment of gastric ulcer disease. Many TCAs have been evaluated for their antiulcer eŠects, but there are presently no data in the literature speciˆcally concerning the antidepressant opipramol. This study aimed to investigate the antiulcer eŠects of opipramol and to determine its potential relationship with oxidant and antioxidant systems. The antiulcer activities of 25, 50 and 100 mg/kg opipramol have been investigated on indomethacin-induced ulcers in rats. Compared with a control group (indomethacin alone), opipramol decreased indomethacin-induced ulcers signiˆcantly at all doses used (52%, 71% and 76% respectively). Opipramol also signiˆcant-ly increased the glutathione (GSH), superoxide dismutase (SOD) and nitric oxide (NO) levels in the stomach tissue, all of which were decreased in the control group given only indomethacin. All doses of opipramol also signiˆcantly decreased myeloperoxidase (MPO), malondialdehyde (MDA) and catalase (CAT) levels in stomach tissue compared to the control. In conclusion, the activation of enzymatic and non-enzymatic antioxidant mechanisms, as well as the inhibition of some toxic oxidant mechanisms, appear to play a role in the antiulcer eŠect of opipramol. This new indication for opipramol prompts a rethinking about the possible clinical application of opipramol, particularly for peptic ulcer patients also presenting depression.