¹College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, CHINA DOI : 10.9775/kvfd.2017.18282 Fibroblast Growth Factor 21 (FGF21) is a novel metabolic regulator involved in lipid utilization, and it can involve in the regulation of lipid metabolism. To determine the physiological function of FGF21 in relation to a high-fat diet (HFD) and high cholesterol, the effect of FGF21 on immune response indicators and hematological parameters was investigated. In the experiment, a total of 24 female mice were selected, 12 of which were fed with HFDs (group 1) and the other were fed with normal diet (group 2). After 30 days, the mice of two groups were respectively divided into two groups on average: 1. HFDs mice were used as model group; 2 normal diet mice were used as control group; 3. HFDs mice injection were used as model + FGF21 group; 4. normal diet injection were used as control+FGF21 group. Mice were sacrificed at 3-day intervals and the livers were isolated and analyzed. Blood was collected and analyzed for CD3 and CD19 by flow cytometry and IL-4, IL-6 and TNF-α by ELISA. Serum TG, TC, NEFA, LDL-c, and HDL-c levels were measured by automatic biochemical analyzer. Although CD3 and CD19 varied, the difference was not significant, and the levels of IL-4, IL-6, TNF-α, TC, TG LDL-c, and NEFA in the model exogenous injection FGF21 group were lower than in the model group (P<0.05). The present results indicate that exogenous FGF21 regulates IL-4, IL-6 and TNF-α and protects the liver from inflammation damage induced by high dietary fat and cholesterol. Keywords : Exogenous FGF21, High-fat diets, Cholesterol, Immunological factor