OBJECTIVE Gestational diabetes mellitus (GDM) is the glucose intolerance occurring during pregnancy. The prevalence of GDM is increased in obese women. Leptin and adiponectin are adipokines that play an important role in the regulation of insulin secretion and glucose and lipid metabolism. The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and the development of GDM. METHODS This case-control study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation. To discriminate the ADIPOQ rs266729, rs1501299 and LEP rs2167270 alleles, TaqMan® Pre-Designed SNP Genotyping Assays were used. RESULTS There was a statistically significant association between the ADIPOQ rs266729 gene polymorphism and GDM. Among women with GDM, a higher prevalence of the G allele was observed (GG and CG genotypes). Multivariate logistic regression analysis, taking into account age, BMI before pregnancy, past pregnancies and the ADIPOQ rs266729 gene polymorphism, revealed that the presence of a G allele is an independent risk factor for GDM. Moreover, there was the association between the LEP rs2167270 polymorphism and the requirement for daily insulin, which was significantly higher in women with the A allele (AA and GA genotypes). CONCLUSIONS The results of our study suggest an association between adiponectin gene rs266729 as well as leptin gene rs2167270 polymorphisms and GDM.