Objective To investigate the influence of metformin on AMP-activated Protein Kinaseα2 (AMPK α2) expression in adipose tissue and oxidative stress indices in diabetic rats, so as to understand the possible mechanism of metformin in improving blood glucose control, oxidative stress and insulin-resistance. Methods Totally 32 male SD rats were randomly divided into normal control (NC) group (n=12), model (T2DM) group (n=10) and metformin group (n=10). Rat model of T2DM was established by high fat/high glucose diet (one month) and intraperitoneal injection of streptozotocin (30 mg/kg). Animals in the metformin group were given 50 mg/(kg·d)( i.g.), and those in the other two groups were given same dose of 0.5% HPMC solution. The body masses of rats were determined before and after treatment. The fasting blood glucose (FBG), fasting insulin (FINS), superoxide dismutase (SOD), glutathione (GSH), N-acetyl-beta-D-glucosaminidase (NAG), malonaldehyde (MDA), myeloperoxidase (MPO), monoamine oxidase (MAO), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) levels were measured by ELISA and Biochemical Analyzer; the ratio of fat to body weight and insulin sensitivity index (ISI) were calculated. RT-PCR was used to evaluate the expression of AMPK α2 mRNA in the adipose tissues. Results Compared with DM group, metformin group had significantly higher AMPK α2 mRNA expression, serum GSH, SOD, ISI and HDL, and significantly lower serum FINS, FBG, NAG, MDA, MPO, MAO, TC, TG and LDL (P<0.05). ConclusionMetformin can increase AMPK α2 expression in the adipose tissue of diabetic rats, regulate glucose metabolism, and improve insulin sensitivity and oxidative stress.