To observe the effects of Huanglian Jiedu Decoction (HLJDD), a traditional Chinese compound herbal medicine, on p85 mRNA and protein expressions of phosphatidylinositol-3-kinase (PI-3K) in target tissues (skeletal muscular and adipose tissues) in rats with type 2 diabetes mellitus (T2DM) and to investigate the molecular mechanism of HLJDD in treating T2DM. The male Wistar rats were injected with streptozotocin (STZ) 30 mg/kg through tail vein, and fed with high-fat and high-caloric diets to induce T2DM. Then the rats were randomly divided into untreated group, aspirin-treated group and HLJDD group, and treated correspondingly. Meanwhile, a group of normal animals without any treatment was set up for normal control group. Ten weeks later, serum fasting blood glucose (FBG), serum fasting insulin (FINS) and oral glucose tolerance test (OGTT) were routinely determined. The expressions of PI-3K p85 mRNA and protein in skeletal muscle and adipose tissue were determined with RT-PCR and Western blotting before and after insulin treatment. Compared with the untreated group, the FBG and OGTT levels in T2DM rats treated with HLJDD decreased significantly (P<0.05). The FINS in HLJDD group was lower than that in the normal control group (P<0.05), but was not significantly different from that in the untreated group. The PI-3K p85 mRNA and protein expressions in HLJDD group obviously increased, as compared with those in the untreated group. The effect of HLJDD in treating T2DM was probably associated with its improvement of PI-3K p85 mRNA and protein expressions in skeletal muscle and adipose tissue of the T2DM rats.