Abstract: Objective To observe the protective effects of dipeptidyl peptidase Ⅳ inhibitor on early diabetic nephropathy patients and to explore the mechanism of renal protection. Methods Total 120 patients suffered with Diabetic nephropathy Ⅲ were randomly divided into test group 1,test group 2,and control group,40 cases in each group.All patients were treated with losartan potassium tablets 50 mg qd+Metformin Sustained Release Tablets 0.5 g bid for 4 weeks.On this basis,the test group 1 plus sitagliptin phosphate tablets 50 mg qd;test group 2 plus sitagliptin phosphate tablets 100 mg qd; the control group were treated with gliclazide MR 30 mg bid. Results Twenty-four weeks after treatment,BMI,FPG,2HPG,HbA1c were significantly decreased compared with before treatment of the three groups(P<0.05).Compared to the control group,the mAlb,urine protein/creatinine ratio,serum cystatin C of test group 1 and test group 2 were all significantly lower than those of the control group at the same time(P<0.05).The test group 2 decreased more significantly than the test group 1(P<0.05).After treatment,hs-CRP,IL-6,TNF-α,NF-κB p65 phosphorylation levels of the three groups were significantly decreased,and these factors of test group 2 were significantly lower than that of the test group 1(P<0.05).Correlation analysis showed that mALB and BMI,FPG,2hPG,HbA1c had no significant correlation(P>0.05),and hs-CRP,IL-6,TNF-α,NF-κB p65 phosphorylation levels were significantly positively correlated(P<0.01). Conclusion The protective effect of phosphate on renal function is independent of the hypoglycemic effect.It is possible to reduce the release of inflammatory cytokines by inhibiting the inflammatory state of the body,which can further improve the inflammatory damage of the kidney and protect the kidney,and the effect is dose dependent.