Introduction: Oxidative stress is caused by the imbalance between production of pro-oxidants and the antioxidant defenses. Reactive oxygen species (ROS) can play an important role in the pathogenesis of cardiovascular diseases. The present study aimed at investigating whether administration of oxytocin ameliorates oxidative stress induced by experimental myocardial infarction in rats. Materials and Methods: Cardiac ischemia-reperfusion (I/R) was induced by occlusion of left main coronary artery of rats for 25 min, followed by a period of reperfusion for 2h. OT at doses of 0.0001-1 μg was administered intraperitoneally 30 min prior to ischemia. Following reperfusion, blood samples were taken for measuring the plasma MDA levels, as an index of lipid peroxidation. Results: We observed a dose-dependent association between dose of oxytocin and plasma MDA. Oxytocin 0.01μg significantly reduced MDA levels as compared to control group. Blockade of specific OT receptors by atosiban attenuated the anti-oxidative effect of OT. The MDA level in the L-NAME and atropine groups were higher than those in the OT group and reach to control group, whereas the MDA levels in the anantin group were same as OT group and significantly lower than those in the control group. Conclusions: Oxytocin has a beneficial effect, mediated by NO and Ach, on cardiac tissue against oxidative damage due to I/R, suggesting that oxytocin can be used to tissue protection against oxidative stress.