ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia pallida is an evergreen endemic tree, mentioned in Ayurveda as the fruits of Terminalia pallida are excellent in cardioprotective property. Tribal people use Terminalia pallida fruit for the treatment of diabetes and this plant widely used in many other disorders. AIM OF STUDY: The present investigation was to evaluate the antioxidant, biochemical profile and histological studies of qualitatively standardized ethanolic extract of Terminalia pallida fruits (TpFE) against isoproterenol-induced myocardial infarction in rats. MATERIALS AND METHODS: TpFE was standardized by high performance liquid chromatography (HPLC) and mass spectroscopy (MS). Rats were pretreated orally with different doses of TpFE (100, 300, and 500mgkg(-1) body weight) and cardioprotective positive control gallic acid (GA) for 30 days prior to isoproterenol (ISO) induced myocardial infarction. The rats were sacrificed, hearts were collected and homogenized for biochemical analysis. The effects on total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), lipid peroxidation (LPO) marker, malondialdehyde (MDA), creatine kinase (CK), lactate dehydrogenase (LDH), alanine transaminase (ALT), aspartate transaminase (AST), catalase (CAT), glutathione peroxidase (GPx), sodium potassium (Na(+)/K(+)), calcium (Ca(2+)) and magnesium (Mg(2+)) adenosine triphosphatases (ATPases) were estimated in heart tissue homogenate. RESULTS: Rats administered with ISO showed a significant increase in TC, TG, LDL-C, VLDL-C, and MDA and a significant decrease in HDL-C, cardiac marker enzymes - CK, LDH, ALT and AST. ISO significantly reduced antioxidants - CAT, GPx, and membrane bound enzymes - Na(+)/K(+), Ca(2+) and Mg(2+) ATPases. Pretreatment with TpFE (100, 300, and 500mgkg(-1) bw) and GA (15mgkg(-1) bw) for a period of 30 days significantly inhibited the effects of ISO. Moreover, biochemical findings were supported by histopathological observations. CONCLUSION: The present study provide evidence for the first time, that TpFE pretreatment ameliorated myocardial injury in ISO-induced myocardial infarcted rats and exhibited cardioprotective activity.