Totally 68 studies with 115,809 subjects were included for analyses, the pooled analyses showed that TCF7L2 rs7903146 (dominant model: p < 0.0001, OR = 0.66, 95% CI 0.63–0.70; recessive model: p < 0.0001, OR = 1.64, 95% CI 1.56–1.73; over-dominant model: p < 0.0001, OR = 1.27, 95% CI 1.21–1.34; allele model: p < 0.0001, OR = 0.71, 95% CI 0.68–0.74) polymorphism was significantly associated with susceptibility to T2DM in overall population. This evidence concerns the gene TCF7L2 and type 2 diabetes mellitus.