Background and Aims: The aim of this study was to determine the association of single nucleotide polymorphism rs1501299 in the ADIPOQ gene with body weight, insulin resistance, serum adipokine levels and metabolic syndrome (MetS). Methods: The study involved a population of 1,007 adult obese subjects. Parameters like body weight, fat mass, waist circumferences, blood pressure, fasting blood glucose, C-reactive protein, insulin concentration, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile and adipocytokines levels (leptin, adiponectin and resistin) were all measured. The genotype of ADIPOQ gene polymorphism (rs1501299) was evaluated. Results: Insulin levels (GG: 13.6 ± 5.1 mUI/l vs. GT: 14.1 ± 5.2 mUI/l vs. TT: 16.6 ± 5.2 mUI/l; p < 0.05) and HOMA-IR (GG: 3.3 ± 1.5 units vs. GT: 4.1 ± 1.1 units vs. TT: 4.5 ± 1.3 units; p < 0.05) were higher in T-allele carriers than they were in non-T-allele carriers. Total adiponectin levels (GG: 20.2 ± 2.4 ng/dl vs. GT: 15.8 ± 3.4 ng/dl vs. TT: 13.7 ± 1.4 ng/dl; p < 0.05) were lower in T-allele carriers than they were in non-T-allele carriers. Logistic regression analysis indicated that subjects with T allele were associated with an increased risk of MetS (OR 1.15, 95% CI 1.08-1.25, p = 0.033) and an increased risk of hyperglycemia (OR 1.99, 95% CI 1.37-2.55, p = 0.028) after adjusting by age and gender. Conclusions: These data suggest an important role of this ADIPOQ variant at position +276 on insulin resistance, total adiponectin levels and MetS.