Objective To study the relationship between the C677T polymorphisms of N5,N10-methylenetetrahydrofolate re-ductase(MTHFR)gene and type 2 diabetic nephropathy(T2DN).Methods By using PCR-RFLP method,the C677T polymor-phisms of MTHFR was analyzed in 163 cases of type 2 diabetes mellitus(T2DM),which included diabetic nephropathy(DN group, n=82)and diabetes without complications(DM group,n=81),and 77 cases of healthy people as the control group(CON).Plasma total Hcy levels were also measured for all the subjects.Results The frequencies of MTHFR TT and CT homogenetic type and al-lele T(4.9%,37.8%,23.8%)in the DN group were significantly higher than those in the DM(2.5%,28.4%,16.7%)group or the CON group(0.0%,29.8%,14.9%).However,there was no significant difference in MTHFR genotype and allele frequency be-tween the DM group and the CON group.Moreover,plasma Hcy levels were markedly higher in the patients with allele TT and CT genotype than those in the patients with CC genotype,the difference showing statistical significance (P <0.01).The univariate lo-gistic regression analysis showed that the C677T polymorphism of MTHFR gene was closely associated with the development of DN.The odds ratio was 1 .660 and the 95% confidence interval was 1.038 and 2.655 respectively.Conclusion The C677T polymor-phisms of MTHFR gene is associated with T2DN in Southeast Guangxi and the allele T might be the susceptibility gene for DN.