Background: Myocardial Infarction (MI) is one of the most common cardiovascular diseases. Curcumin has been used in traditional Chinese and Indian medicine to treat a variety of diseases. It is safe and effective due to its anti-oxidant and anti-inflammatory properties. Aim of the Work: This study was conducted to investigate the possible protective role of curcumin oral administration in experimental MI induced by isoproterenol (ISO) using biochemical and histological techniques. Materials and Methods: This study was carried out on thirty-two male adult albino rats, divided into four equal groups. Group I was the normal control group. Group II was a sham control group that was divided into two subgroups: IIa and IIb, four rats each; they received distilled water and curcumin respectively. Group III received  ISO. Group IV received both curcumin and ISO. Animals of all groups were sacrificed one day after the last dose of ISO. The serum cardiac  marker enzymes Creatine Kinase (CK) and its myocardial isoenzyme (CK-MB) were estimated. Specimens from the left ventricle were subjected to light and electron microscopic studies. Results: There was significant increase in serum CK and CK-MB in ISO-treated group compared to the control and sham control groups. Treatment with curcumin before ISO decreased significantly these enzymes. Isoprotrenol administration resulted in foci of separation and fragmentation of the muscle fibers. There was no distinction between the dark and light bands and obscured Z lines. Some of the fragmented cardiomyocytes lost their nuclei while others revealed pyknotic or distorted nuclei. Mononuclear cell infiltration, areas of  haemorrhage, severe edema and cellular homogenicity were observed. Mitochondria appeared variable in size and shape. They were swollen and less in number as compared to the control sections. Administration of curcumin before ISO showed sound organization of the muscle fibers similar to that of control sections and minimal mononuclear cell infiltration. The mitochondria were of similar number to the control group but they were swollen and showed ruptured membranes and cristae. Conclusions: curcumin administration minimized elevation of plasma cardiac enzyme markers CK and CK–MB following experimental myocardial injury by ISO administration and preserved the normal histological architecture of the myocardium. This beneficial effect of curcumin was mostly related to its antioxidant and anti-inflammatory properties