Salinomycin is an ionophore compound that may be used in sheep as growth promoter or to prevent coccidiosis in these species. There are some reports with respect to the poisoning of animals with this agent used in high concentration in feed by mistake. So, the purpose of this study was to examine the gross and histopathologic lesions due to salinomycin in sheep. Fifteen adult (4 to 5 years old) male Mehraban sheep were randomly divided into three equal groups and doses of 1, 2, and 4 mg/kg of salinomycin were administrated orally twice a day for 2 days. Five sheep died due to acute toxicosis within 72 h after administration of the drug. Postmortem examination revealed congestion and edema of skeletal muscles, swelling and hemorrhage in peripheral lymph nodes, hydrothorax, and hydropericardium, petechial hemorrhage in fat tissues of heart base, severe pulmonary congestion and edema, large pale kidney, and swelling of liver with mild to moderate yellowish appearance. Histopathologic examination showed pulmonary congestion and edema with hyalinized thrombi in some of capillaries, myocardial degeneration, and necrosis without any inflammatory reaction. Hepatocytes, renal tubules, sciatic nerves, and muscles were among other tissues that showed histologic changes.