Silybum marianum extract (SME) has been used for centuries as a natural remedy for diseases of liver and biliary tract. Lately, it has been promoted as a nutritional supplement for beneficial effects on some risk factors of diabetes and hyperlipidemia. In this study we aimed to determine the effects of SME for on high-fat diet (HFD) induced metabolic disorders. Male Sprague Dawley rats were fed HFD for 11 weeks to induce obesity. SME was given to animals for two different durations, for 11 weeks or for 7 weeks. The results showed significant increase in plasma transaminases, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), leptin, high sensitive c-reactive protein (hsCRP), glucose and insulin along with significant increase in body mass index (BMI) and liver weights in rats fed the HFD diet compared to rats fed with standard rat diet. SME supplementation for different durations raised improvement in the HFD-induced metabolic disorders such as insulin resistance, hyperlipidemia and hepatopathy at different degrees. Our study concludes that SME can be well considered as an effective supplement to improve insulin and leptin sensitivity and hyperlipidemia and to suppress body weight gain.