Recently, many studies have investigated the association of allelic variants of Wolfram syndrome gene (WFS1) with insulin secretion, insulin sensitivity and the risk of hyperglycemia and type 2 diabetes (T2D). Although it is clear that WFS1 mutations cause diabetes, the genetic basis of the association of common WFS1 variants with T2D is still unclear. To date, many case-control studies have been carried out to investigate the role of the WFS1 gene polymorphism in the development of T2D. However, these studies are controversial and individual studies may have insufficient power to reach a comprehensive and reliable conclusion. The aim of this study was to investigate association of WFS1 genes polymorphisms (rs734312 and rs10010131) with T2D by conducting a meta-analysis. Seven studies with 6705 T2D cases and 11144 controls were enrolled in the meta-analysis of the association between rs734312 polymorphism and T2D, and 12 studies with 16304 T2D cases and 22004 controls were enrolled in the meta-analysis of rs10010131 polymorphism. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed and random-effects models. Heterogeneity among studies was evaluated using the I² and Begg's test was used to evaluate publication bias. Sensitivity analysis was also performed. Our results suggested that the G allele of rs734312 polymorphism [dominant: FEM OR 0.873, 95%CI (0.810 - 0.940), recessive: FEM OR 0.876, 95% CI (0.800 - 0.959)] and A allele of rs10010131 polymorphism [dominant:FEM OR 0.853, 95% CI (0.817 - 0.892), recessive:REM OR 0.833, 95% CI (0.756 - 0.917)] in WFS1 gene had significant protective effects on risk of T2D.