Lycopene, a potent antioxidant provides protection against free radicals and has been used in the treatment of cancer, coronary heart disease and hypercholestrimia. Losarton has been used for the treatment of essential hypertension, cardiac hypertrophy and various cardiovascular disorders. The present study was designed to evaluate the cardioprotective effect of combination of Losartan with Lycopene in isoproterenol induced cardiomyopathy in rats. Myocardial infarction was induced by isoproterenol (ISO, 85 mg/kg, sc) twice at an interval of 24 hrs in Wistar rats. ISO produced significant alteration in the hemodynamic parameters (Blood pressure and heart rate), creatine kinase, lactate dehydrogenase, TBARS, GSH, SOD and catalase. Oral treatment with losartan (10 mg/kg) and lycopene (4 mg/kg) for 21 days in ISO treated rats attenuated above mentioned parameters. The treatment with combination of losartan and lycopene reduced the cardiotoxicity induced by ISO which was confirmed by reduction in hemodynamic parameters, TBARS, LDH, CK and increase in GSH, SOD and Catalase enzymes. The effect could be due to the myocardial membrane protection provided by antioxidant and free radical scavenging property. Thus, combination therapy with losartan and lycopene provides new intervention in the treatment of cardiomyopathy.