Objective To explore the relationship between the rs3760106 (C/T) variation of protein kinase C-β gene (PRKCB1) and type 2 diabetic end-stage renal disease (ESRD). Methods Shanghai Han patients with type 2 diabetes were selected and divided into the end-stage renal disease of diabetic nephropathy group (DN-ESRD group)(n=174) and non-diabetic nephropathy group (the DN-0 group)(n=228). The genotypes of rs3760106 were detected by the Taqman PCR assay. Frequencies of genotypes and alleles of rs3760106, as well as clinical characteristics of two groups were compared and analyzed. Results The differences of frequencies of genotypes and alleles of rs3760106 of the DN-0 group and DN-ESRD group were statistically significant (P<0.05). The risk of incidence of DN-ESRD for people with CT+TT genotype significantly increased with OR of 2.14 (95%CI, 1.18-3.87). After sex, onset age of diabetes, and BMI correction, the risk of incidence of DN-ESRD for people with CT+TT genotype still existed. For the DN-0 group or DN-ESRD group, the fasting plasma glucose (FPG) level of people with CT+TT genotype was significantly higher than that of people with CC genotype (P<0.05) or had an increasing tendency (P>0.05). Conclusion The risk of incidence of ESRD for Shanghai Han patients with type 2 diabetes mellitus who carry T allele of rs3760106 of PRKCB1 gene is high.