Objective  To investigate the relationship between rs2576178 mutation of renalase gene (RNLS) and the incidence of hypertension of type 2 diabetic nephropathy patients with micro-albuminuria. Methods  A total of 225 type 2 diabetic nephropathy patients with micro-albuminuria (DN group, all Han nationality) and 251 healthy controls (control group) were enrolled. The DN group was further divided into the DN-HTN(+) group (combined with hypertension, n=169) and DN-HTN(-) group (not combined with hypertension, n=56). The genotype of locus rs2576178 of RNLS gene of subjects was detected by the Taqman PCR assay. The differences of genotypic and allelic frequencies and clinical variables between two groups were compared. Results  The genotype distribution of rs2576178 of DN group and control group was consistent with Hardy-Weinberg equilibrium. Compared with the control group, AA genotypic and A allelic frequencies of the DN group significantly decreased (P<0.05). AA genotype of rs2576178 significantly correlated with hypertension after sex, age, and BMI of all subjects were corrected by non-conditional Logistic regression analysis with OR of 0.48 (95%CI: 0.28-0.81). Compared with the DN-HTN (-) group, GG+GA genotypic and G allelic frequencies significantly increased in DN-HTN(+) group (P<0.05). AA genotype of rs2576178 significantly correlated with hypertension after sex, age, and BMI of the DN group were corrected with OR of 0.37 (95%CI: 0.17-0.79). Conclusion  AA genotype of rs2576178 of RNLS may decrease the incidence of hypertension of type 2 diabetic nephropathy patients with micro-albuminuria.