Objective: To investigate the effects of peripheral leptin infusion on metabolism in ventromedial hypothalamus (VMH) lesioned obese rats. Methods: Four groups were prepared: (1) VMH lesioned rats with infusion of leptin, (2) VMH lesioned rats with infusion of saline, (3) sham VMH lesioned rats with infusion of leptin and (4) sham VMH lesioned rats with infusion of saline. After VMH lesion and sham operations, a mini pump filled with either leptin or saline was implanted into the back of rats. Body weight and food intake were recorded daily. Seven days later, all rats were sacrificed after overnight fast. Blood samples were collected for determination of glucose, triglyceride, total cholesterol, insulin and leptin. Perimetric fat pad (PFD) was isolated and weighed. Pancreas was embedded by paraffin and sectioned, and performed by immunostaining with proliferating cell nuclear antigen (PCNA) for study of the proliferative activity of insular cells. Results: In sham operated groups, food intake and increased body weight decreased significantly in rats with leptin infusion than those without leptin infusion. No similar findings were observed in VMH lesioned rats. Plasma insulin, triglyceride and total cholesterol in the rats with leptin infusion regardless of VMH lesion or sham operations were decreased when compared with their controls. In respect to PFD, two VMH lesioned groups did not differ, but two sham operated groups differed. Positive PCNA rate in VMH lesioned rats receiving leptin declined significantly. Conclusion: Leptin regulations of food intake, body weight and body fat are dependent upon intact VMH. Peripheral infusion of leptin decreases plasma triglyceride and total cholesterol in VMH lesioned rats.