Aim The expression of α3 subunit of nicotinic acetylcholine receptor (α3nAChR) has been demonstrated in aorta, adipocyte and macrophage.The objective of the present study was to verify the regulatory roles of α3nAChR in the inflammatory responses of atherosclerosis.Methods The inflammatory indicators were detected in mouse macrophage, adipocytes and mouse aortic endothelial cells (MAECs) after the α3nAChR was antagonized or after the α3nAChR gene was silenced.Meanwhile, atherogenesis was induced in the apolipoprotein E knockout(ApoE/) mice after fed with an atherogenic highfat diet for 7 weeks.Results In MAECs, the lipopolysaccharide (LPS)stimulated secretions of the adhesion molecules and inflammatory cytokines were significantly enhanced(30% ~ 80%) after pretreatment with αConotoxin MⅡ (an antagonist for α3nAChR) or after knockdown withα3nAChR gene.In adipocytes, the knockdown of α3 gene promoted the generations of the proin? Ammatory adipokines or cytokines but decreased the production of adiponectin, an antiinflammatory adipokine, by 29.29 ±9.43%.In macrophage silenced with α3nAChR gene, the M1 (classical) activation was predominantly stimulated, whereas the M2 (alternative) activation was suppressed.In addition, the amount of the atherosclerotic lesions and the infiltration of the M1 type activated macrophages into the arterial wall were markedly elevated in the αConotoxin MⅡtreated ApoE/mice.Conclusion The α3nAChR may play a pivotal role in regulating the atherogenesis through influencing the inflammatory responses of Ecs, macrophages and adipocytes.The mechanisms involve the regulations of multiple cell signaling pathways.