Resistin, which appears to be related to insulin resistance, is secreted mainly from macrophages in human and some of its polymorphisms have been reported. Based on recent in vitro studies, resistin may be associated with atherosclerosis by mediating endothelial hyperactivity. We investigated whether resistin polymorphism at -420C>G is associated with serum resistin levels and diabetic macroangiopathy (coronary heart disease, arteriosclerosis obliterans, and stroke) in 349 Japanese type 2 diabetic patients (DM) and 286 non-diabetic controls (non-DM). Serum resistin levels in DM with a history of stroke were significantly higher than those without, 19.6+/-2.1 and 12.4+/-0.5 ng/ml (P<0.001), respectively. Furthermore, the levels were significantly increased in a genotype-dependent manner (CC, CG, GG) based on the polymorphism at -420C>G (P<0.001) in both DM and non-DM. The prevalence of stroke in DM significantly increased according to the presence of mutations (P<0.035). In multivariate logistic-regression analysis, individuals with the CG or GG genotypes were significantly more likely to have had a stroke than individuals with the CC genotype (vs. CG; OR 2.99, P=0.024, vs. GG; OR 4.49, P=0.010). These data suggested that the genotyping of resistin polymorphism at -420(C>G) can be a risk marker for stroke susceptibility in Japanese type 2 diabetic patients.