Objective：To investigate the effect of 11β-hydroxysteroid dehydrogenase1（11β / HSD1）on glycolipid abnormalities and its role in the development and progression of obesity and insulin resistance. Methods：The adipocyte-specific-11β/HSD1 knockout mice were constructed firstly. Five mice of 5 weeks-old adipocyte-specific-11β/HSD1 knockout mice and C57BL/6 mice were selected separately to establish the model of obesity（DIO）induced by high-fat diet. After feeding 5 and 6 weeks，mice were processed intraperitoneal glucose tolerance test（IPGTT）and insulin tolerance test（ITT），respectively. Mice were sacrificed after feeding 12 weeks，and the weight of body and visceral fat were measured，hematoxylin-eosin staining（HE）was subsequently used to assess the degree of fat vacuoles change. The levels of blood glucose，triglyceride，cholesterol，urea and creatinine were also detected. Expression of 11β/HSD1 and some markers associated with glycolipid metabolism were analyzed by Western blotting and quantitative real-time PCR. Results：The adipocyte-specific-11β/HSD1 knockout mice were constructed successfully. There was no significant difference in body weight，visceral fat weight between the two groups，but the adipocyte-specific-11β/HSD1 knockout mice decreased concentrations of serum glucose and size of adipocyte，and increased glucose tolerance and insulin sensitivity，compared with the control group. The protein levels of 11β/HSD1 and transcription factors peroxisome proliferator-activated receptor gamma（PPAR-γ） and CCAAT enhancer-binding proteins alpha（C/EPB-α） were obviously lower in the adipose tissues of adipocyte-specific-11β/HSD1 knockout mice than that of the control group. Conclusion：The down-regulation of 11β/HSD1 expression in adipose tissues can reduce the lipid droplets deposition and improve the insulin sensitivity in DIO.