Background: Methylenetetrahydrofolatereductase (MTHFR) is a regulatoryenzyme of homocysteine metabolism. Point mutation in MTHFR andhyperhomocysteinemia are implicated in the pathogenesis of diabeticnephropathy (DN) in many ethnic groups. The aim of this study is to find ifMTHFR C677T polymorphism is a risk factor of DN in type 2 diabetes mellitus(T2DM) patients.Subjects and methods: The MTHFR C6777T polymorphism was detected in122 T2DM patients by PCR-RFLP. They were divided into 3 groups; 75 patientswith normoalbuminuria, 33 patients with microalbuminuria and 14 patients withmacroalbuminuria. Seum levels of homocysteine (HCY) were determined bynephelometry.Results: The presence of MTHFR 677T allele increases the risk ofmacroalbuminria 2.6 folds (p=0.009) in T2DM patients. The presence of mutantgenotypes CT and TT increase the risk of macroalbuminuria 3.7 folds(p=0.02).Serum levels of HCY were not associated with C677T mutation(p=0.22), also there was no significant association between high levels of HCYand DN (p=0.05).Conclusion:Methyl tetrahydrofolatereductase (MTHFR) C677T gene mutationwas associated with increased risk for overt diabetic nephropathy in type 2diabetic patients and had no effect on serum levels of homocysteine.