Abstract: Objective To explore the relationship between the levels of serum cystatin C (CysC), retinol binding protein (RBP) and urinary N- acetyl beta -D Glucosaminidase (NAG) changes and the severity of diabetic nephropathy in diabetic patients with renal microvascular lesions. Methods 30 cases of type 2 diabetic patients with nephropathy (urinary albumin<14.29mg/L) as group A, 30 cases of type 2 diabetic patients with nephropathy (urinary albumin≥ 14.29mg/L) as group B, 30 cases of type 2 diabetic nephropathy uremia patients as group C and 30 normal subjects as group D were involved in this study. The serum levels of CysC, RBP and urine NAG in all groups were determined. Results There were significantly difference on the levels of serum CysC, RBP and urine NAG between four groups (P <0.01). The levels of serum CysC, RBP and urine NAG in group A, group B and group C were significantly higher than those in group D (P <0.05). The levels of serum CysC, RBP and urine NAG in group A and group B were significantly lower than those in group C (P <0.05). The levels of serum CysC, RBP and urine NAG in group A were significantly lower than that of in group B (P <0.05). Conclusion The levels of serum CysC, RBP and urinary NAG in diabetic patients with renal microvascular lesions show an increase tendency as the severity of diabetic nephropathy increasing.