Background and aim: Insulin resistance is one of the main features of both polycystic ovary syndrome (PCOS) and type 2 diabetes. Several polymorphisms in genes related to insulin action have been demonstrated to be associated with type 2 diabetes mellitus (T2DM). However, less is known about the association of such susceptibility genes for T2DM with PCOS. Methods: We therefore compared 57 women with confirmed PCOS to a control cohort of 567 nondiabetic healthy female women from our Tübinger Family Study database. All subjects were genotyped for common polymorphisms in the adiponectin gene exon 2, Pro12Ala in PPAR(2, CAPN10 SNP 43, 44 and 45, Gly972Arg in IRS-1, Gly1057Asp in IRS-2, human winged Helix/ Forkhead transcription factor FOXC2 promotor region. To determine glucose tolerance a standard 75g WHO OGTT was performed. Insulin sensitivity index was estimated from the OGTT. Results: In PCOS-women compared to controls, we found a statistically significant difference in 2-hr glucose (6.5±0.2 vs. 6.0±0.06, p=0.03), fasting insulin (79±7.1 vs. 53.4±1.8, p=0.02), insulin sensitivity estimated from the OGTT (12.4±1.1 vs. 19.1±0.5, p=0.0001), serum triclyceride (138±11 vs. 105±3, p=0.003), serum HDL (50±2 vs. 61±1, p=0.0001) and serum testosterone (62±5 vs. 41±1, p=0.01), after adjusting for age and % body fat. In women with PCO syndome we found a significantly higher number of homozygous carriers of the T allele of T-G polymorphism in adiponectin exon 2 after adjusting for age and % body fat (2.6% vs.13%, p=0.007). All other polymorhisms tested showed no significant association with PCOS (all p>0.5). Conclusion: In women with PCOS characterised by insulin resistance and features of the metabolic syndrome, we found an increased frequency of the T-G polymorphism in the adiponectin exon 2 gene. However, other common polymorphisms in genes related to insulin resistance and type 2 diabetes showed no association to PCOS.