Objective To investigate the levels of serum cystatin C(Cys C)and homocysteine (Hcy) in the patients with type 2 diabetic nephropathy(DN), and to clarify their clinical significances. Methods 100 patients of type 2 diabetes mellitus(T2DM) were divided into three groups according to Mogenson staging: simple diabetes mellitus group(DM,n=32),early DN group (EDN,n=40),clinical DN group(CDN,n=28).The healthy subjects were defined as control group(n=20).The following variables were detected by automatic biochemical analyzer:HbA1c,serum biochemistry indexes,Cys C and urinary albumin excretion rate(UAER);the serum Hcy level was measured by circulate enzymatic determination method;the glomerular filter rate (GFR) and endogenous muscle liver clear rate (Ccr) was calculated;the indexes of weight,height,waist circumference,DBP,SBP of all subjects were measured;the influence factors of Cys C,Hcy, and UAER were analyzed by correlation analysis;the positive rates of Cys C,Hcy, and UAER were detected in various groups. Results As the extension of T2DM duration,compared with control group,the levels of SBP,HbA1c,and TC of the diabetic subjects were increased significantly (P<0.05).The levels of UAER,BUN,Scr,Cys C,and Hcy were gradually increased of the patients in diabetes groups.The levels of UAER,BUN, and Hcy of the patients in DM group were higher than those in control group(P<0.05);the levels of UAER,BUN,Cys C and Hcy of the patients in EDM group were higher than those in control group(P<0.05),and the levels of UAER,Cys C,and Hcy were significantly increased compared with DM group(P<0.05);compared with EDN group,the levels of UAER,BUN,Scr,Cys C, and Hcy of the patients in CDN group were increased(P<0.05);compared with control group,the levels of UAER,BUN,Scr,Cys C, and Hcy of the patients in DM group were increased(P<0.05);the levels of GFR and Ccr of the patients in DM group were gradually decreased,and were higher than those in control,DM,and EDN groups(P<0.05).The correlation analysis results showed that the serum Cys C level was positively correlated with diabetes duration,UAER,Hcy,Scr,BUN,HbA1c and SBP(r=0.61,r=0.804,r=0.597,r=0.516,r=0.487,r=0.423,r=0.359,P<0.01),and negatively correlated with GFR and Ccr(r=-0.652,r=-0.589,P<0.01);the level of Hcy was positively correlated with diabetes duration,UAER,Scr,BUN,HbA1c and SBP(r=0.673,r=0.784,r=0.502,r=0.396,r=0.416,r=0.209,P<0.01),and negatively correlated with GFR and Ccr(r=-0.623,r=-0.647,P<0.01).The partial correlation analysis results showed that UAER had the most significant relationship with Cys C(r=0.789,P<0.05),then with Hcy(r=0.697,P<0.05),and had general relationship with Scr and BUN (r=0.472,r=0.543,P<0.05).The positive rates of Cys C and Hcy of the patients were higher than the positive rates of Scr and BUN in EDN group(P<0.05). Conclusion Both of serum Cys C and Hcy are able to reflect early renal damage.Cys C is more sensitivity and has clinical value in early diagnosis of DN and being a kidney injury marker.Joint detection of serum Cys C and Hcy can evaluate the renal function and prognosis of DN patients.