The paper is to study the effect of fibroblast growth factor-21 (FGF-21) on lipid metabolism in the monosodium glutamate (MSG) induced obese rats. SD rats were induced by MSG after weaning, and then randomly divided into experimental and vehicle groups. After fed to 20 weeks, the experimental groups were injected with FGF-21 (1 mg/kg) for a continuous 32 d. The rats were detected the body weight, Lee's index, food intake, abdominal and subcutaneous fat content, lipid content, glucose tolerance and the relevant indicators of hepatic and lipid metabolism before and after the injection. As compared to vehicle-treated rats, FGF-21 did not affect the amount of daily food intake in MSG rats, but led to a significant reduction in Lee's index, total body weight and abdominal fat mass (52.8% reduction) at the end of treatment. After FGF-21 treatment, the levels of glucose, triglycerides, cholesterol and LDL-C decreased except HDL-C. The exogenous FGF-21 led to the improvement of the liver weight, hepatic AST, ALT and ALP and the reduction of endogenous FGF-21, PPARα and PPARγ in liver. In summary, FGF-21 could regulate on lipid metabolism and reverse hepatic steatosis in MSG rats.