Abstract: Objective To study the relation between rs1078533 polymorphism of IRS-1 gene and clopidogrel resistance (CR) in Chinese patients with type 2 diabetes mellitus (DM) accompanying coronary artery disease (CAD). Methods Three hundred and twenty-five patients with type 2 DM accompanying CAD admitted to General Hospital of Shenyang Military Area Command from April 2012 to April 2013 were enrolled in this study. Their residual platelet aggregation rate (RPA) induced by 20μmol/L adenosine diphosphate (ADP) was measured by optical nephelometry. The CR was defned when the RPA was ≥70%. The patients were divided into CR group (n=142) and non-CR group (n=183) according to their RPA. The genotypes and allele frequencies at rs1078533 of IRS-1 gene in two groups were detected by PCR and pyrophosphate sequencing, respectively. Results The genotype frequencies at rs1078533 of IRS-1 gene conformed to the Hardy-Weinberg equilibrium in two groups. The frequency of genotypes (AA, AC and CC) was 1.4%, 16.8%, 81.8%, respectively, in CR group and 1.6%, 19.8%, 78.6%, respectively, in non-CR group. No significant difference was observed in genotypes and allele frequencies between the two groups (P= 0.786 and P= 0.524). Logistic regression analysis revealed that the rs1078533 polymorphism was not related with the CR after adjustment of risk factors including age, gender, BMI, smoking and hypertension in patients with type 2 DM accompanying CAD. Conclusion The rs1078533 polymorphism of IRS-1 gene is not related with the CR in patients with type 2 DM accompanying CAD．