Insulin receptor substrate-1 is the first and key substrate of the insulin receptor, act as a multisite docking protein for various effector molecules. It is encoded by the IRS-1 gene, which is found on chromosome 2q36.3 in humans. Insulin receptor substrate is an effective insulin signaling agent that plays a key role in preserving the cell’s basic function, any polymorphism in the IRS genes acts as a competitive insulin receptor inhibitor. A total of 150 healthy men as control and 200 diabetic patients participated in this study; it is across-sectional study, patients were chosen while seeking medical care in the outpatient clinic. This study investigates the association of IRS-1 rs2943641 to the pathogenesis of type 2diabetes mellitus in Iraqi males. This study was conducted to study the association of SNP rs2943641[TT(minor allele type), TC(heterozygous alleles type) and CC(major allele type)] to the pathogenesis of type 2diabetes mellitus according to the logistic regression method which demonstrates that there is a significant association between TC and CC allele groups to the pathogenesis of T2DM. In conclusion, genetic polymorphism of IRS-1 rs2943641 is associated with the pathogenesis of T2DM in Iraqi male.