BackgroundAdipose tissue is an important endocrine organ that secretes a number of adipokines, like Resistin (RETN); it's an adipocytes‐secreted cytokine and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity was controversial. This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) inRETNgene 420C/G; 44G/A; 62G/A; 394C/G and 299 G/A and their association with Resistin level and obesity in Tunisian volunteers.MethodsWe recruited 169 nonobese (mean age=42.16‐14.26 years; mean body mass index [BMI]=24.51‐3.69 kg/m2) and 160 obese (mean age=47.86‐11.17 years; meanBMI=36‐4.78 kg/m2). Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism. Anthropometric parameters, lipid levels, Glycemia and insulinemia were measured,BMIwas calculated and insulinresistance was evaluated with the homeostasis model assessment insulin resistance (HOMA‐IR) and resistin level was measured byELISA. Statistical analyses were performed bySPSS19.0.ResultsAfter adjustment for confounding parameters; the Odds Ratio (OR) of obesity associated with mutated genotypes at 420C/G compared with normal genotype was as:OR=2.17; 95%CI[1.28‐3.68],P=.004. The serum Resistin levels present no significant association with allRETNpolymorphisms and it was significantly associated withBMI(P=.047). In our haplotype analysis, one haplotype seems to be protective and one other seems to be the highest risk to obesity.ConclusionThe 420 C/G Polymorphism were associated with obesity and Leptin concentration in our population.