Objective To observe the effect of paeoniflorin on insulin resistance in rats fed with high-fat diet and to investigate the possible mechanisms.Methods Male Sprague Dawley (SD) rats were randomized into 4 groups:normal control,high-fat diet,high-dosage paeoniflorin (HDP group),and lowdosage paeoniflorin (LDP group).The control group was fed with ordinary diet,while the others with highfat diet,paeoniflorin intervention groups were given low-or high-dosage paeoniflorin by intraperitoneal injection.After 6 weeks,fasting serum triacylglycerol (TG),total cholesterol (TC),free fatty acids (FFA),fasting blood glucose (FBG),and insulin were determined.Insulin sensitivity index (ISI) were calculated and then the animals were sacrificed to acquire epididymal fat mass.The tumor necrosis factor alpha (TNFα) and glucose transporter 4 (Glut4) expressions in adipose tissue were detected by quantitative realtime polymerase chain reaction(PCR).Results Compared with high-fat fed group,HDP group had lower epididymal fat pad weight,reduced level of FBG,insulin and FFA (P ＜0.05) and improved ISI(-5.84 ± 0.24 vs-6.44 ± 0.25,P ＜ 0.05).LDP group had similar trends.In adipose tissue,the TNFα expression in LDP and HDP group was lower,Glut4 expression in HDP group was higher than that of high-fat fed group (P ＜ 0.05).Conclusion Paeoniflorin can reduce visceral adipose content,inhibit TNFα expression and increase Glut4 expression in adipose tissue,eventually lower glucose,and improve insulin resistance caused by high-fat diet.