Resistin is an adipocyte-secreted cytokine recently discovered and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity and metabolic syndrome (MetS) was controversial. Our aim was to study the relationship between four resistin polymorphisms (420C/G, 44G/A, 62G/A, and 394C/G), MetS parameters, and the risk of obesity in Tunisian volunteers. We recruited 169 nonobese (sex ratio=0.594; mean age=43.25±13.12 years; mean body mass index [BMI]=24.73±3.50 kg/m(2)) and 160 obese subjects (sex ratio=0.221; mean age=48.41±10.92 years; mean BMI=36.6±4.8 kg/m(2)). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. Anthropometric parameters, lipid levels, glycemia, and insulinemia were measured. BMI was calculated and insulin resistance was evaluated with the homeostasis model assessment insulin resistance (HOMA-IR). Statistical analyses were performed by SPSS 17.0. The 420C/G seems to contribute to obesity. In fact adjusted odds ratio (OR) of obesity associated to mutated genotypes was 2.17 and 95% confidence interval was 1.28-3.68 (p=0.004). Mutated genotypes at 420C/G were associated with higher waist circumference and BMI. In addition, 44G/A polymorphism was associated with increased total cholesterol and low-density lipoprotein-cholesterol levels. The other genotypes showed no association with MetS parameters. Concerning association between single-nucleotide polymorphisms and MetS risk, only mutated genotypes at 44G/A increase the risk of MetS after adjustment to confounding parameters (OR=1.93, p=0.023). In conclusion, resistin gene polymorphisms 420C/G and 44G/A were associated with obesity and MetS parameters in Tunisian volunteers.