Type 2 diabetes mellitus (T2DM) is a chronic disease caused by genetic and environmental factors. T2DM has been associated with specific polymorphisms in the TCF7L2 gene. This study evaluates the relationship between the rs7903146 locus polymorphism of the TCF7L2 gene and T2DM susceptibility through meta-analysis; the overall aim is to provide a basis for evidence-based medicinal treatment of T2DM. Cohort and case-control studies from Medline, PubMed, EMBASE, CBM, CNKI, and academic conferences/dissertations that examined the correlation between T2DM and rs7903146 polymorphisms were evaluated. We determined whether the TCF7L2 rs7903146 locus was associated with T2DM susceptibility by comparing alleles and genotypes. The Stata 11.0 software was applied for meta-analysis, and a random-effects model was adopted for heterogeneity testing and odds ratio (OR) calculation. A fixed-effect model was used for quantitative analysis of the heterogeneity between different studies, and for calculating the percentage of variability I(2). A total of 10 studies related to the rs7903146 loci and T2DM susceptibility were enrolled; this included 3404 cases of T2DM patients and 6473 control cases. Meta-analysis showed that the T allele of rs7903146 was significantly correlated with the risk of T2DM, with both a dominant fixed-effect model (OR = 1.653, 95%CI = 1.416-1.653) and a co-dominant-fixed effect model (OR = 1.525, 95%CI = 1.350-1.723). Meta-analysis revealed that the T allele of rs7903146 was also correlated with T2DM susceptibility.