Objective To compare the anti-inflammatory effect of Carbocisteine alone or combined with Budesonide in the airway epithelial cell model, and identify the regulatory mechanisms. Methods MTT method was used to determine cell survival rate after treatment with cigarette smoke extract (CSE). After various drugs and inhibitor/stimulator treatment, ELISA was used to detect the inflammatory factor levels, Western blot was used for determination of ERK and IκBα proteins, and RT-PCR was used to detect the transcription abundance of ERK and NF-κB. Results The model group showed significant elevation of inflammatory factors, increased ERK and IκBα protein abundance, and upregulation of ERK and NF-κB mRNAs. Although treatment with Carbocisteine and glucocorticoid respectively showed anti-inflammatory effect, no statistical significance was detected when these two drugs were combined. Further study showed the significant decrease of p-ERK protein and ERK mRNA and NF-κB mRNA abundance after Carbocisteine and the inhibitor (PD98059) treatment. The effect was partially reversed by the application of the stimulator (EGF). Conclusions Carbocisteine has similar anti-inflammatory mechanism as glucocorticoid. Combination of these two drugs doesn’t show significant synergistic effect due to suppression of the same signal transduction pathway.