The potential suppression role of cordycepin(Cor)on airway remodeling in a rat model of chronic asthma was investigated in this paper.We evaluated the anti-remodeling of Cor(50mg/kg)combined with or without budesonide(BUD)and investigated the possible underlying molecular mechanisms.We found that Cor attenuated immunoglobulin(Ig)E,alleviated the airway wall thickness,and decreased eosinophils and neutrophils in the bronchoalveolar lavage fluid(BALF).Notably,Cor reduced the up-regulation of IL-5,IL-13 and TNF-α in the BALF.Cor also regulated the increase of A2AARmRNA and the decrease of TGF-β1 expression.Furthermore,Cor markedly blocked p38MAPK signaling pathway activation in the OVA-driven asthmatic mice.The combination treatment of Cor and BUD showed profound efficacy in regulating the levels of inflammatory cells and the expression of IL-13,TGF-β1 and A2AARmRNA.Collectively,this study demonstrated that Cor combined with glucocorticoids treatment shows synergistically profound efficacy in inhibiting airway remodeling,and some benefits of Cor may result from the increased A2AARmRNA expression,the reduced TGF-β1 levels and the inhibition of Th2-cytokines through the suppression of the p38MAPK signaling pathways.