The cardioprotective potential of Inula racemosa root hydroalcoholic extract against isoproterenol-induced myocardial infarction was investigated in rats. The rats treated with isoproterenol (85 mg/kg, s.c.) exhibited myocardial infarction, as evidenced by significant (P < 0.05) decrease in mean arterial pressure, heart rate, contractility, relaxation along with increased left ventricular end diastolic pressure, as well as decreased endogenous myocardial enzymatic and non-enzymatic antioxidants. Isoproterenol also significantly (P < 0.05) induced lipid peroxidation and increased leakage of myocyte injury marker enzymes. Pretreatment with I. racemosa extract (50, 100 or 200 mg/kg per day, p.o.) for 21 consecutive days, followed by isoproterenol injections on days 19th and 20th significantly (P < 0.05) improved cardiac function by increasing the heart rate, mean arterial pressure, contractility and relaxation along with decreasing left ventricular end diastolic pressure. Pretreatment with I. racemosa also significantly (P < 0.05) restored the reduced form of glutathione and endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase from the heart, which were depleted after isoproterenol administration. In addition to restoration of antioxidants, I. racemosa significantly (P < 0.05) inhibited lipid peroxidation and prevented the leakage of myocytes specific marker enzymes creatine phosphokinase-MB and lactate dehydrogenase from the heart. Thus, it is concluded that I. racemosa protects heart from isoproterenol-induced myocardial injury by reducing oxidative stress and modulating hemodynamic and ventricular functions of the heart. Present study findings demonstrate the cardioprotective effect of I. racemosa and support the pharmacological relevance of its use and cardioprotection mechanism in ischemic heart disease as well as substantiate its traditional claim.