This study was designed to assess the effects of saffron (Crocus sativus) on rats' heart with isoproterenol-induced myocardial injury. Animals were divided randomly into four groups: vehicle-control group (CTL); ISO group, administrated with Isoproterenol 85 mg/kg s.c.; saffron group; and finally combined Saffron + ISO group. Basal and final serum levels of heart troponin I, heart tissue antioxidants and histopathological indices were assessed in all groups. Isoproterenol administration significantly increased serum level of troponin I when compared to control group (3.46 +/- 0.77 vs. 0.53 +/- 0.35 ml in ng/ml, P < 0.001) and reduced significantly the glutathione peroxidase activity of heart muscle (1.63 +/- 0.21 vs. 4.01 +/- 0.64 nmol/mg protein, P < 0.05). The grade of heart muscle damages was severe in more than 70% of ISO group animals. Saffron + ISO group showed remarkably decreased intensity of tissue destruction and significantly decreased serum levels of heart troponin I, when compared to ISO group (1.25 +/- 0.23 vs. 3.46 +/- 0.77 ng/ml, P < 0.05). The level of glutathione peroxidase activity in Saffron + ISO animals did not have significant decline compared to saffron alone. These results suggest the protective role of saffron on ischemic hearts by biochemical and histopathological findings.