Previous studies regarding the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and diabetic nephropathy (DN) risk in Caucasian individuals with type 2 diabetes reported conflicting results. To derive a more precise estimation of this association, a meta-analysis was performed.Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association between MTHFR C677T polymorphism and DN risk. Finally, 10 case-control studies with a total of 1590 DN cases and 1555 type 2 diabetic controls without DN were included.Overall, there was an association between MTHFR C677T polymorphism and increased risk of DN under four comparison models (OR T vs. C=1.50, 95% CI 1.07-2.02, P=0.02; OR TT vs. CC=2.09, 95% CI 1.07-4.08, P=0.03; OR TT vs. TC+CC=1.70, 95% CI 1.10-2.63, P=0.017; OR TC+TT vs. CC=1.85, 95% CI 1.19-2.88, P=0.006). Sensitivity analysis suggested exclusion of any single study did not materially alter the overall pooled ORs above.This meta-analysis supports that there is an association between MTHFR C677T polymorphism and DN risk, and MTHFR 677T variant contributes to increased risk of DN in Caucasian individuals with type 2 diabetes.