Background: Astragaloside IV (AST) is a saponin from the roots of Astragalus plants which has been widely used in traditional medicine to treat cardiovascular diseases. However, the effect of AST on myocardial infarction remains unknown. Thus, we aimed to investigate the cardio protective effects of AST on isoproterenol-induced myocardial infarction in rats. Methods: AST was isolated from the roots of Astragalus caspicus. Male Wistar rats were assigned to 5 groups of control, isoproterenol, and treatment with 2.5, 5 and 10 mg/kg AST given orally immediately before MI induction. Subcutaneous injection of isoproterenol (100 mg/kg) for two consecutive days was used to induce myocardial infarction. AST was given orally once daily for 4 days. On the fifth day hemodynamic and electrocardiographic parameters were assessed, and serum and tissue samples were used to evaluate histological and biochemical changes. To more assessment of the effects of AST on myocardium, we also used three doses of 0.1, 1 and 2 µM of AST in isolated heart model. In statistical analysis with one-way-ANOVA test, any differences between groups were considered significant at p<0.05. Results: Isoproterenol injection caused ECG abnormality, hemodynamic depression and myocardium damage. While AST administration increased mean arterial blood pressure and heart rate and improved the left ventricular contractility. The peripheral neutrophil count, cardiac enlargement and cardiac ischemia was significantly decreased by AST. Also, histopathological evaluations showed that AST significantly diminished post MI necrosis and fibrosis in heart tissue and inhibited the inflammatory responses. The isolated heart studies hemodynamic factors showed no significant changes. Conclusion: Results showed that AST can protect heart against myocardial infarction by improving cardiac histology and ventricular contractility. Due to the lack of protection in the isolated heart, it is likely that the positive effects are more associated with the improvement of the oxidative stress markers in the systemic circulation, and the absolute effect on the isolated heart does not play an essential role in myocardium protection.