To observe the effect of Shihu Compound (DC) sequential therapy on gene expression of protein of hepatic insulin signal pathways in db/db mice and to discuss the molecular mechanism of regulating blood sugar. Methods:Eighteen male db/db mice of 12~14 weeks old were randomly divided into model group, metformin group, and DC group according to FBG and body mass. Six db/m mice were taken as normal control group. They were given by continuous gavage for 6 circles (54 d). OGTT were measured at the end of the experiment. The concentrations of FBG, GSP, insulin, TG and Tch in sernm were measured, and the expression of insulin receptor， insulin receptor substrate 1/2 and PI3K in liver were assayed RT-PCR. Results:Compared with model group, FBG, Ins and GSP in DC group and metformin group decreased significantly (P<0.05), and glucose tolerance improved (P<0.05~0.01). The level of mRNA expression on InsR, IRS1/2 and PI3K were increased. Conclusion:Dendrobium Compound sequential treatment effectively reduced glucose and lipid， and improved glucose tolerance in db/db mice,which could be associated with increased the expressions of components in the insulin signal pathway, such as InsR, IRS1/2 and PI3K．