The present study was designed to examine the phyto-constituents and cardioprotective activity of Pongamia pinnata (PP) leaf extract (hydro-alcoholic) in experimentally induced myocardial infarction in Wistar Albino rats. Six groups of Wistar albino rats, each comprising six animals, were selected for this study. Group I served as a control, Group II rats were given isoproterenol (20 mg/100g, subcutaneously), and Group III rats were given Pongamia pinnata leaf extract (300 mg/kg). Groups IV, V and VI rats were given Pongamia pinnata leaf extract (100 mg/kg, 200 mg/kg and 300 mg/kg, respectively) and isoproterenol (20 mg/100g subcutaneously) prior to MI induction. The transaminases (aspartate transaminase and alanine transaminase), lactate dehydrogenase (LDH) and creatine phosphokinase (CK), were estimated in both the plasma and heart tissues. Troponin T activity was separately estimated for plasma. Isoproterenol significantly increased the activities of CK, LDH and the transaminases in plasma with a concomitant decrease in these enzymes in tissue. Pretreatment with the hydro-alcoholic leaf extract of Pongamia pinnata at a dose of 300 mg/kg body weight for 30 days had a significant effect on the activities of marker enzymes compared to the other groups. Pongamia pinnata pretreatment may offer protection in experimental cardiotoxicity induced by isoproterenol. Phytochemical screening of the plant leaves reveals the presence of carbohydrates, alkaloids, flavonoids glycosides, steroids, tannins and saponins.