〔Abstract〕 Objective To study the mechanism of saxagliptin in alleviating insulin resistance in diabetic rats by miR-15 a-5 p/insulin receptor(INSR) axis. Methods Firstly the intersection of miRNA that might target INSR was sellected from Targetscan, miRDB and miRWalk by inputing the transcript of INSR ENST00000341500. Then dual luciferase reporter assay was used to verify the targeting relationship. Subsequently the insulin resistance-type 2 diabetes mellitus(IR-T2 DM) models were constructed. Then, IR-T2 DM rats were treated with miR-15 a-5 p mimic, miR-15 a-5 p inhibitor or saxagliptin. Rats were sacrificed after 8 weeks to obtain quadriceps femoris muscles and peripheral blood. Blood pressure, blood glucose, lipid metabolic parameters, homeostasis model assessment(HOMA) insulin resistance index(IRI) as well as insulin sensitivity index(ISI) were measured in each group, respectively. Quantitative PCR was used to detect the expression of intersection miRNA and IRS-1, IRS1, GLUT4 mRNA while Western blot was adopted to test the protein expression of INSR, p-IRS-1 and GLUT4 in skeletal muscle of rats in each group. Results miR-15 a-5 p was selected as the targeting miRNA of INSR. Compared with negative control group, the expression of INSR, IRS-1 and GLUT4 in skeletal muscle as well as the concentration of HDL-C, BW and ISI in peripheral blood of IR-T2 DM rats treated with miR-15 a-5 p inhibitor or saxagliptin markedly increased( P<0. 5),but the concentration of hemoglobin A1 c( Hb A1 c),triglyceride( TG) and low-density li Poprotein cholesterol( LDL-C),systolic blood pressure( SP),diastolic blood pressure( DP) and IRI in peripheral blood significantly increased in the above two groups( P<0. 05). The trend of the above indexes in miR-15 a-5 p mimic group was completely opposite to that in miR-15 a-5 p inhibitor and saxagliptin group( P<0. 05). In addition,saxagliptin combined with miR-15 a-5 p inhibitor had more effictive capacity in relieving insulin resistance than treating the diabetic rats with saxagliptin or miR-15 a-5 p inhibitor alone( P<0. 05). Conclusion Based on the results observed during this study,the paper shows that saxagliptin has distinct effect on relieving insulin resistance by down regulating miR-15 a-5 p to up regulate INSR expression in diabetic rats.