Though there are studies to show protective effect of glutathione against neurotoxicity and nephrotoxicity, the present study was designed to investigate the cardio protective effect of glutathione against isoproterenol induced myocardial infarction in rats by demonstrating the changes in serum cardiac markers, antioxidant enzymes and ECG changes. Wistar male rats were randomly divided into four groups namely control (GI), glutathione (GII), isoproterenol (GIII) and glutathione + isoproterenol treated (GIV). Glutathione treated group-received glutathione (200 mg/kg body wt) orally for 30 days. Myocardial infarction was induced in rats by isoproterenol administration (100 mg/kg) subcutaneously (sc) at an interval of 24 hrs on 31st and 32nd day cardiac marker enzymes, ECG, lipid peroxidation and antioxidant enzymes were assessed 24 hrs after the last dose of isoproterenol. Isoproterenol showed changes in ECG pattern, increase in serum level of cardiac marker, increased lipid per oxidation and decreased antioxidant defense system in heart. Glutathione pretreatment brings almost all the parameters to near normal level in isoproterenol-induced myocardial infarction in rats. The present study revealed that glutathione ameliorates cardiac damage in isoproterenol induced myocardial infarction in rats due to potent antioxidant, free radical scavenging effect, myocardial adaptation at cellular and organ levels.