Glutathione S-transferases protect cells against exogenous and endogenous oxidative stress. Type 2 diabetes is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This study investigated whether GSTA1*A/*B and GSTP1Ile105Val polymorphisms could affect the risk for type 2 diabetes. A cross-sectional case-control analysis included 468 (326 men and 142 women) Japanese participants in a health screening program. The prevalence of type 2 diabetes was 11.3% (63 subjects: 52 male and 11 female). The frequency of GSTA1*B allele carriers was higher in diabetes than in non-diabetes, though the difference was not statistically significant (adjusted OR, 1.8; 95% CI, 0.9-3.4). The risk among the GSTA1*B allele carriers was significantly increased by current-smoking status (adjusted OR, 3.7; 95% CI, 1.1-12.7; vs. never-smoking non-carriers), whereas the smoking status was not an independent risk factor. The GSTP1 genotype alone or in combination with the smoking status did not affect the risk for diabetes. This is the first report to show that the GSTA1*B allele is a potential risk factor for smoking-related type 2 diabetes.