To investigate whether the insulin receptor substrate (IRS)-2 G1057D polymorphism is associated with the risk of endometriosis, and to evaluate potential correlation of IRS2 gene polymorphism with the stages of endometriosis.Case-control study.Gynecology clinics in university hospital.Women with (n = 135) or without (n = 135) endometriosis. Afterward, the women with endometriosis were divided into two groups according to the stage: group 1 included 63 women in stages I-II, and group 2 included 72 women in stages III-IV.Genotyping by polymerase chain reaction-based restriction fragment-length polymorphism method.Genotype distribution of the G1057D polymorphism in the IRS2 gene.The genotype distribution of the IRS2 G1057D polymorphism in the endometriosis group was significantly different from that of the control group (GG/GD/DD rates were 43.0%/39.3%/17.7% and 55.6%/36.3%/8.1% for the endometriosis and control groups, respectively). Further subgroup analyses according to the stage of endometriosis also revealed a positive association between the IRS2 DD genotype expression and stage III-IV endometriosis patients in the population studied.These results suggest that the IRS2 G1057D polymorphism may be associated with an increased risk for endometriosis.