Atopic dermatitis (AD) is a common skin condition that affects both children and adults. Adipokines have been shown to play a role in the pathogenesis of AD. In the current study, the association between adiponectin gene (ADIPOQ) polymorphisms and AD was investigated. In addition, changes in serum adiponectin levels in AD patients were examined. Restriction fragment length polymorphism-PCR technique was used to genotype ADIPOQ SNPs. The ELISA assay was used to measure serum Adiponectin levels. A total of 324 participants (162 AD and 162 healthy controls) were included in the study. The frequency of the GG genotype of rs3774261 was higher in the AD group (44.5%) than in the control group (32.7%, P<0.05). Regarding the rs2241766 SNP, the frequency of the GG genotype was higher in the AD group (10.5%) than in the control group (3.1%), while the frequency of the TT genotype was lower (P<0.001) in the AD group (35.8%) than the control group (57.4%). Moreover, the GG haplotype of rs3774261 and rs2241766 significantly increased the risk of AD by about 2-fold (P<0.05). Finally, serum adiponectin levels were lower in the AD group than in the control group (P<0.05). These results indicate an association of the rs2241766 and rs3774261 SNPs with the risk of developing AD among the population examined.