Introduction: Gestational diabetes mellitus is a multi-factor disease. Several genes are shown to be associated with diabetes mellitus. Among them, IRS-1 gene is located on chromosome No.2 which is an endogen substrate for insulin receptor. IRS-1 gene has an important role in insulin pathway signaling. Aim of this study was to review the association of Ala513Pro and Gly972Arg IRS-1 gene polymorphism with gestational diabetes mellitus in south of Iran. Methods: 200 subjects with gestational diabetes mellitus and 200 healthy subjects as control group were enrolled in the study. DNA was extracted from their blood and polymorphism of G, C and T allele were studied. It was aimed to investigate whether genotype is associated with clinical and biochemical variables such as family history, fasting blood sugar, blood lipid and body mass index. Independent sample t- test, chi- square test, logistic regression and Hardy- Weinberg equilibrium tests were used to analyze data (p≤0.05). Results: The finding from the Polymorphism Gly972Arg study show that individuals with CC, CT genotypes were associated with an increased risk of the disease (%95CI: 0.02-0.44, OR=0.1, P<0.001), (%95CI:2-58.43, OR=9.2, P<0.01). There was no allele and genotypic variation in Polymorphism Ala513Pro Polymorphism. Conclusion: Based on the obtained results, Ala 513Pro polymorphism of the IRS-1 gene was not correlated, but Gly 972 Arg polymorphism related with gestational diabetes mellitus in population of south Iran. پرونده مقاله