Studies have provided evidences for the effects of nicotine on adipose tissues, as well as in inflammatory response. We hypothesized that nicotine affects adipokine gene expression in adipose tissues via specific neuronal nicotinic acetylcholine receptors (nAChRs). First, we described the expression of multiple nAChR subunit genes in mouse white and brown adipose tissues (WAT and BAT), and detected differential expression in WAT and BAT (alpha2>alpha5>beta2 and alpha2>beta2>beta4, respectively). Additionally, when nicotine was administered to wild-type mice, it significantly affected the expression of adipokine genes, such as Tnfalpha, AdipoQ, Haptoglobin and Mcp1 in WAT. Next, we demonstrated that in mice deficient for the beta2 nAChR subunit (beta2-/- mice), the expression levels of Cox2 and Ngfbeta genes in WAT, and Leptin, Cox2, AdipoQ and Haptoglobin in BAT, were significantly altered. Furthermore, interactions between mouse beta2 subunit and nicotine treatment affected the expression levels of the adipokine genes Tnfalpha, Cox2 and AdipoQ in WAT and of AdipoQ in BAT. Finally, analysis of a cellular model of cultured adipocytes demonstrated that application of nicotine after silencing of the beta2 nAChR subunit significantly elevated the expression level of Cox2 gene. Together, our data suggest a molecular link between the beta2 nACh receptor subunit and the expression levels of specific adipokines, which is also affected by nicotine.