Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, with multiple genetic and environmental factors involving in its etiology. ACE and eNOS gene were considered to have important roles in the development and progression of DN. In this study, a case-control study was carried out to investigate the effects of 7 SNPs in ACE gene and 2 SNPs in eNOS gene in the development of DN in Northern China.7 SNPs including A240T, A2350G, A5466C, A2215G, T3892C, C1237T and C3409T of ACE gene and 2 SNPs (G894T and T786C) of eNOS gene were genotyped by polymerase chain reaction restriction fragment length polymorphism method. 431 type 2 diabetic patients with nephropathy (cases) were compared to 420 type 2 diabetic patients without nephropathy (controls) in the study. Data were analyzed by SPSS 17.0 and HaploView software. The frequency distribution of A2350G, 4 haplotyps in ACE gene and G894T in eNOS gene were demonstrated to be different between case and control groups significantly. Whereas other SNPs and haplotypes had no differences in two cohorts. The results revealed that variations of ACE and eNOS gene had association with DN, which indicated ACE and eNOS gene may play an important role in pathogenesis of DN in Northern Chinese Han population.