11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), one of the isoforms of the 11beta-hydroxysteroid dehydrogenase enzymes, acts as an oxo-reductase to reactivate cortisone to cortisol, plays a critical role in tissue-specific corticosteroid reactions, and is therefore a key molecule associated with the development of metabolic syndrome. We investigated whether variations in the 11beta-HSD1 gene correlated with metabolic syndrome. We performed case-control study using a population-based urban Japanese cohort. Among 3005 urban residents, we examined 431 subjects diagnosed with metabolic syndrome according to the Japanese definition and 777 subjects with none of metabolic syndrome criteria as control. We genotyped three single nucleotide polymorphisms (SNPs) (+9410T>A, +17925C>T, +27447G>C) across the 11beta-HSD1 gene in them and analyzed the associations of SNPs and haplotypes with metabolic syndrome. The +9410A allele showed a tendency to metabolic syndrome (OR=1.5, 95%C.I., 1.0-2.2; P=0.041 and Bonferroni corrected P=0.123) without statistical significance. However, we could not find any significant association between metabolic syndrome and SNPs in the 11beta-HSD1 gene. Our findings indicate that polymorphisms and haplotypes in the 11beta-HSD1 gene are not significantly associated with metabolic syndrome in the Japanese population.