The aim of this study was to investigate the changes and correlations of plasma Homocysteine (Hcy) and serum Cystatin C (Cys C) under different urinary albumin excretion rates in diabetic nephropathy. According to the 24 h urinary albumin excretion rate, 90 type 2 diabetes patients were divided into three groups: normal albuminuria group (n=27), microalbuminuria group (n=37), and macroalbuminuria group (n=17); 30 healthy subjects were included as controls. Fasting plasma glucose, glycosylated hemoglobin, triglyceride, cholesterol, serum creatinine, Hcy, and Cys C levels were determined, and the bivariate correlation analysis was used for linear correlation analysis. The Hcy values of the three groups were 8.46 ± 2.72, 9.43 ± 2.13, and 13.52 ± 5.24, respectively; these values were significantly different (P<0.01). The Cys C values of the three groups were also significantly different (P<0.01). As urine albumin excretion and aggravated glomerular filtration function increased, Hcy and Cys C levels also increased, showing a positive correlation (r=0.641, r=0.892, and r=0.765, P<0.01 in three groups, respectively). Combined detection of Hcy and Cys C can be used to predict the impacts of Hcy on glomerular filtration function and degree of renal damage of diabetic nephropathy. Blood Hcy levels should be evaluated at an early clinical stage.