The protective effect of ethanolic leaf extract of Ipomoea biloba in isoproterenol (ISO)-induced cardiotoxicity and the antioxidant activity involved in this protection were investigated in rats. Myocardial infraction was produced in rats with 20 mg/kg b.wt of ISO administered subcutaneously twice at an interval of 24 h. Effect of EEIB oral treatment for 28 days at two doses (100 mg and 200 mg/kg body weight) was evaluated against ISO – induced cardiac necrosis. Level of enzymatic (SOD, CAT, GPx and GST), non-enzymatic (GSH, Vitamin C and E) and of membrane bound ATPases (Na+K+ATPase, Mg2+ATPase and Ca2+ATPase) were assayed in heart homogenate. Significant myocardial infarction, depletion of endogenous antioxidants enzymatic and non-enzymatic were observed in ISO-treated animals when compared with the normal animals. Rats induced with ISO, showed a significant (P<0.05), decrease in the activities of GSH, Vitamin C and Eon comparison with normal rats. EEIB elicited a significant cardioprotective activity by elevated the levels of GSH, SOD, CAT, GPx and GR. A significant decrease in the activity of Na+/K+ ATPase and a corresponding increase in the activities of Ca2+ ATPase and Mg2+ ATPase were observed in isoproterenol induced rats when compared to normal control rats. Pretreatment with EEIB was able to efficiently prevent the increase in activity of Mg2+ ATPase and maintain the activities of Na+ /K+ ATPase and Ca2+ ATPase at near normality. There is no significant difference between the control and plant alone treated rats. The aim of this investigation is to evaluate the antioxidant effects on the main cardioprotective activity of ethanolic leaf extract Ipomoea biloba.