Insulin resistance has been a possible underlying pathophysiologic defect inducing the metabolic syndrome (MS). However association studies regarding Insulin receptor gene in different ethnic groups are scarce in literature. Here we conduct an association study between MS and genetic polymorphism of the INSR gene in Yi and Han Chinese. In a cross-sectional study, 3,436 Yi and Han people were investigated. Ethnicity-specific case-control studies were designed, with MS patients diagnosed as cases and non-MS people as controls matched on gender and age. Polyrnerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of the exon 8 of the INSR gene. Data were analyzed using one-way analysis of variance, chi-square test, and logistic regression where appropriate. Systolic blood pressure (SBP) was significantly higher in MS patients with the N1N2/N2N2 genotypes than that in those with the N1N1 genotype of both ethnic population (p<0.05). Frequency of the N-2 allele was significantly higher in MS patients than that in controls of ethnic Han (p=0.020). Multivariable logistic regression analysis showed that the NsiI polymorphism of the exon 8 of the INSR was an independent predictor for MS in Han people adjusted for total cholesterol, sex, physical activity, educational level, family income, alcohol intake and smoking (OR=2.55, 95% CI: 1.31-4.94, p=0.006). The results indicated that Nsil polymorphism of the INSR gene is associated with SBP in these two different ethnic groups, and significantly associate with MS in Han Chinese. These findings contribute to our better understanding on the genetic basis of MS.