Context: Although many studies displayed the favorable effects of Assafoetida, some of them reported that high doses of Assafoetida could lead to harmful effects. Aims: In this study, the effect of pretreatment with Assafoetida investigated on ischemic-reperfusion injury in isolated rat heart model. Materials and Methods: Thirty two male Wistar rats were divided into 4 groups of eight. Group 1 as the control (Con) group and three other groups as the treatment groups that given Assafoetida by gavage at levels of 25, 50 and 100 mg/kg, once a day for four weeks (T25, T50 and T100 groups). Then their hearts were subjected to 30 min global ischemia and 90 min reperfusion under langendorff apparatus. Results: The data shown that hemodynamic parameters including left ventricular developed pressure (LVDP) and maximum and minimum of pressure changes (±dp/dt) were increased in T25 and decreased in T50 and T100 groups during reperfusion in comparison with Con group. There was not any significant difference in the incidence of irreversible ventricular fibrillation between T25 and Con group, while it was increased in T50 and T100 groups significantly. There was not any significant difference in infarct size between all groups. Conclusion: These data indicate that pretreatment of rats with Assafoetida have cardioprotective effects in low doses and cardiotoxic effects in higher doses. Therefore, it needs more investigation in the future.