Objective To investigate the effects of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor on the rat insulin resistance of diet induced obesity (DIO) and its possible mechanism. Methods Twenty-four female SD rats were selected and randomly divided into the 11β-HSD1 inhibitor group (n=12) and control group (n=12). Each group was further divided into the full diet group (n=6) and high-fat diet group (n=6) according to the diet. After DIO model was established, rats of the 11β-HSD1 inhibitor group were administrated with 11β-HSD1 inhibitor of 20 mg/kg for 10 d, twice a day by gavage and rats of the control group were administrated with normal saline of 20 mg/kg. Rats of the inhibitor group were weighted before and after gavage. The intraperitoneal glucose tolerance test (IPGTT) was then conducted and the changes of blood glucose and insulin sensitivity were observed. Time points of blood collection were 0, 15, 30, 60, and 120 min. Expressions of 11β-HSD1, PPAR-α, PPAR-γ, and GcK mRNA of the liver were measured by the Real-time PCR. Results The results of gavage by 11β-HSD1 inhibitor showed that the weight, blood glucose, and insulin level of the high-fat diet group of inhibitor group were decreased compared to those before gavage. The expression of 11β-HSD1 of the full diet group of inhibitor group was increased. The expressions of PPAR-α, PPAR-γ, and GcK mRNA of the inhibitor group and control group were increased. The increase of the high-fat diet group was more significant than that of the full diet group (P<0.01). Conclusion The 11β-HSD1 inhibitor can decrease the body weight of rats and improve the insulin resistance and sensitivity of DIO rats, which may be relevant to the improvement of glucose utilization and lipid metabolism.