Present study was carried to evaluate the protective effect of Lagenaria siceraria fruit juice (LSFJ) in isoproteranol (ISO) induced myocardial infarction in rats. Rats treated with ISO (200 mg kg-1, s.c.) for two consecutive days at an interval of 24 h resulted in a significant (p<0.001) alteration in cardiac marker enzymes (alkaline phosphatase, Lactate dehydrogenase, creatine kinase-MB, serum Aspartate Transaminase and alanine Transaminase), lipid peroxidation and endogenous antioxidants activities (reduced glutathione, glutathione peroxidase, glutathione s-transferase, superoxide dismutase and catalase). It also showed alteration in electrocardiographic and hemodynamic parameters. Treatment with LSFJ (400 mg/kg/day, p.o.) for 30 days and challenged with ISO on 29th and 30th day showed a protective effect on serum marker enzymes, LPO, endogenous antioxidants activity, electrocardiographic and hemodynamic changes. These finding indicates, protective effect of LSFJ during isoproterenol induced myocardial infarction and associated oxidative stress in rats.