Given that the NcoI polymorphism of the tumor necrosis factor-beta (TNF-beta) gene has been shown to be associated with tumor necrosis factor-alpha (TNF-alpha) secretory capacity, we know that this TNF-beta gene polymorphism may influence insulin resistance. In Caucasians, 2 polymorphisms of the TNF-alpha promoter region (positions -308 and -238) have been reported to be associated with insulin resistance. Thus, we investigated how genetic variation in the TNF-beta and TNF-alpha genes was associated with insulin resistance in 211 Japanese men. The frequency of the TNF-beta gene polymorphism was 0.41, and insulin resistance, estimated by homeostasis model assessment (HOMA), was significantly lower in variant homozygotes versus wild-type allele. The frequencies of the -308 and -238 polymorphisms were 0.01 and 0.02, respectively, and these polymorphisms were not associated with insulin resistance. Our results suggest that the TNF-beta gene polymorphism decreases insulin resistance, and that the -308 and -238 polymorphisms of the TNF-alpha promoter region are not a major contributing factor to insulin resistance in Japanese men.