Abstract： Objective To study the association of insulin receptor substrate 2 (IRS 2) gene codon 1057 g/a polymorphism with type 2 diabetes and its intermediate phenotypes in Chinese Han population in Beijing. Methods The IRS 2 gene codon 1057 g/a polymorphism was detected by polymerase chain reaction and appropriate restriction enzyme (PCR RFLP) in 110 type 2 diabetic cases and 80 normal controls. Results (1) The frequency of allele a was 26.4% in case group and 36.3% in control group. (2) The aa genotype frequency of the polymorphism was significantly lower in the case group than in the control group, 5.5% and 18.7% respectively ( P= 0.016). Logistic regression analysis showed the aa genotype might be a preventive factor of type 2 diabetes, with OR=0.28 (95% CI=0.09 0.91, P= 0.03). (3) No matter in the case group or in the control group, there was no significant difference in blood pressure, blood lipid profile, islet β cell function index or insulin resistant index, etc. among three groups with different genotypes. Conclusion The aa genotype of IRS 2 gene codon 1057 g/a polymorphism has a significantly lower distribution in type 2 diabetes group than that in the control group in northern chinese population, but is not associated with any intermediate phenotypes of type 2 diabetes. The results have to be confirmed by the future study in which the volume of research sample should be enlarged.