Objective: This study aimed to determine the ADIPOQ gene -11377 polymorphism in association with insulin resistance and risk factors of metabolic syndrome (MetS). Methods: We investigated adiponectin gene -11377C>G polymorphism in 156 subjects with MetS and 142 healthy control subjects. The MetS was defined using the modified IDF criteria. The protocol was approved by the Ethics Committee of the Ministry of Health. The -11377C>G polymorphic locus was amplified using the forward primer 5’-ACTTGCCCTGCCTCTGTCTG-3’ and the reverse primer, 5-CCTGGAGAACTGGAAGCTG-3’. A p value < 0.05 was considered statistically significant. Results: The mean age of the patients with MetS was 41.7 ± 11.3 years and that of the controls was 41.2 ± 10.2 years. In people with MetS, the mean fasting insulin, adiponectin, leptin and HOMA-IR, levels were 18.16 ± 19.91 ng/ml, 7.17 ± 3.60 ng/ml, 16.68 ± 13.45 ng/ml and 4.41 ± 6.48 rescpectively. On the other hand, in people without MetS, the mean fasting insulin, adiponectin, leptin and HOMA-IR, levels were 13.01 ± 21.95 ng/ml, 10.05 ± 11.11 ng/ml, 6.92 ± 7.31 ng/ml and 2.41 ± 4.53 rescpectively. The serum adiponectin level and HOMA-IR significantly higher, the serum leptin levels significantly lower in the MetS group (p < 0.05). The adiponectin level positively correlated with age, but negatively correlated with TG, waist circumference, waist hip ratio, diastolic blood pressure, weight and BMI (p < 0.05). With CG and GG (75.04 ± 12.49 mg/dl) of -11377C >G had significantly higher glucose level compared to with the genotype CC (68.85 ± 11.76 mg/dl) in without MetS (OR = 1.071, p = 0.017). With genotype CG and GG (22.43 ± 24.32 ng/ml) of -11377C>G had significantly higher levels of serum insulin than those with the genotype CC (12.97 ± 9.99 ng/ml) in people with MetS (OR = 1.006, p = 0.015). More importantly, we found that with genotype CG and GG (5.70 ± 8.00) of -11377C>G had significantly higher HOMA-IR than those with the genotype CC (2.71 ± 2.83) in people with MetS (p = 0.002). Conclusion: -11377C>G polymorphism was related to the MetS susceptibility, and this polymorphism impacted on circulating glucose, insulin, leptin and insulin resistance.