Objective To explore the potential mechanism of Fangji Huangqi Decoction (防己黄芪汤) in treating insulin resistance (IR).Methods SD rats were randomized into the blank group,the model group,Chinese medicine group and Western medicine group,with 10 rats in each group.Every group was given high-fat diet for 12 weeks to build IR model except the blank group.After modeling,Chinese medicine group was administered Fangji Huangqi Tang (0.6 g/ml) by gavage at a dose of 1 ml/100 g,Western medicine was given Pioglitazone suspension (1mg/ml) by gavage at a dose of 1 ml/100 g and the model group and the blank group were given distilled water of equal volume.The drugs were given for continuous 2 weeks.After modeling,the glucose infusion rate (GIR) of each group was detected;after administration,the volume of free fatty acid (FFA),adiponectin (APN),leptin (LP) and resistin were detected;the ectopic fat deposition level in skeletal muscle was observed by oil red O staining;the volume of AMP-activated Protein Kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK) in skeletal muscle were detected by Western-blotting method.Results Compared with the blank group,the volume of FFA,LP and resistin and the expression of p38 MAPK in the model group were significantly higher,while the volume of APN,GIR and the expression of AMPK were significantly lower (P ＜0.05 or P ＜0.01).Compared with the model group,the volume of FFA,LP and resistin and the expression of p38 MAPK in Chinese medicine group and Western medicine group were significantly lower,while the volume of APN and the expression of AMPK were significantly higher (P ＜ 0.05 or P ＜0.01).The oil red O staining showed that,compared with the model group,the red stained particles in the skeletal muscle of Chinese medicine group and Western medicine group were significantly fewer,and the lipid deposition ameliorated.Conclusion Fangji Huangqi Decoction could improve the IR and the disturbance of lipid metabolism of rats as well as regulating the levels of adipocytokines.It might make these by regulating the expression of proteins in AMPK signaling transduction pathway.