To investigate the effect of Tangzhiping on phosphorylation of IRS-1 and distribution of GLUT4 in skeletal muscle in rats with insulin resistance. Methods: SD rats of total 24 were randomly divided into four groups: Chinese medicine group, western medicine group, control group and model group. The rat model of insulin resistance (IR) was established by feeding with high-fat and high-salt diet. Rats in Chinese medicine and western medicine group were treated with Tangzhiping and metformin respectively for eight weeks. Eight weeks later, western blot test was used to detect tyrosine phosphorylation of IRS-1 and phosphorylation of Akt. Immunofluorescence assay was used to observe distribution of GLUT4 in skeletal muscle. Results: The level of tyrosine-phosphorylated IRS-1and phosphorylated Akt in rats of the model group was significantly lower than that in rats of control group. Treatment of IR rats with Tangzhiping or metformin elevated the level of tyrosine-phosphorylated IRS-1and phosphorylated Akt (P<0.01), when compared with the model group. There was no statistical differences between Chinese medicine group and western medicine group (P>0.05). GLUT4 was distributed predominantly on the membrane of skeletal muscle in rats of control group. GLUT4 distribution on membrane was significantly attenuated and GLUT4 distribution in plasma appeared in skeletal muscle of rats in the model group, which was improved by Chinese medicine and western medicine treatment. Conclusion: Tangzhiping can elevate insulin resistance by promoting the phosphorylation of IRS-1 and its downstream signal Akt and increasing the translocation of GLUT4 from cytoplasm to membrane.