Objective:To investigate the mechanism of Pioglitazone(PGZ) on insulin resistance and type 2 diabetes mellitus by using the DIO(diet-induced obese) mice model. Methods:The C57BL/6J mice were randomly divided into the normal diet group and high-fat diet(HFD) group. After 20 weeks,the obese mice were randomly divided into obese control group,PGZ group. They were orally administered placebo and PGZ[10 mg/(kg·d)] respectively for two weeks. The adiponectin mRNA expression levels from adipose tissue were analyzed by real-time quantitative PCR. The levels of plasma glucose,serum insulin and adiponectin were measured by Biochemistry technology,Radioimmunity and ELISA. The adipocyte sizes were also observed by Immunohistochemistry. Results:The weight,plasma glucose and serum insulin levels increased(P < 0.05) in HFD group,and the adipocyte sizes were bigger. Comparing to obese controls,serum insulin and glucose levels significantly decreased(P < 0.05) and the adipocyte sizes reduced in PGZ treatment group, while plasma adiponectin level raised(P < 0.01). Moreover,the mRNA expressions of adiponectin upregulated(P < 0.05). Conclusion:The effects of PPAR-γ agonist on insulin resistance can be carried out through regulating the expression of adipocytokines.