Hypercholesterolemia, characterized by nitric oxide bioavailability, lipid profile and oxidative stres changes is one of the important risk factors for atherosclerosis. Melatonin secreted by the pineal gland is protective against oxidative stress and endothelial dysfunction. Atorvastatin is a HMG-CoA reductase inhibitor, used in the treatment of hypercholesterolemia. This study was aimed to investigate effects of melatonin and atorvastatin on vaspin, visfatin levels in liver and aorta and serum l-arginin levels in high-cholesterol diet-induced hypercholestremia. Rats were divided into 5 groups (n:7). While control group was fed with normal diet, other groups were fed with % 2 cholesterol and % 0.5 cholic acid diet to develop hypercholesterolemia for 8 weeks. Melatonin was administrated by intraperitoneal injection both concurrently with cholesterol and during last 2 weeks. Atorvastatin (10 mg/kg) was administered by gavage during last 2 weeks. The tissue vaspin and visfatin levels were detected by Western-Blot and serum l-arginin level was measured by HPLC. The changes of vaspin, visfatin levels in liver and aorta tissues and serum l-arginin level were decreased by melatonin and atorvastatin treatments in high-cholesterol diet-induced hypercholestremia. These results suggest that melatonin may have protective and therapeutic effect on hypercholestremia and create similar effects with atorvastatin.