Abstract: Objective：To explore the effect of cigarette smoke extract (CSE) on the differentiation of bronchial epithelial cells and the role of mitogen-activated protein kinase (MAPK)/forkhead box A2 (FOXA2) signaling pathways in this process. Methods：BEAS-2B cells were cultivated and treated respectively with cigarette smoke extract (CSE), CSE and ERK inhibitor U0126, CSE and JNK inhibitor SP600125, CSE and p38 inhibitor SB203580. Thus the blank control group and cigarette smoke extract (CSE) treatment group, CSE+ERK inhibitor U0126 treatment group, CSE+JNK inhibitor SP600125 treatment group, and CSE+p38 inhibitor SB203580 treatment group were set. ELISA was developed for detecting the protein levels of phosphorylated ERK1/2, JNK, and p38. The mRNA and protein levels of FOXA2, E-cadherin, CD44 and ZO-1 were measured by real-time fluorescent quantitative PCR and Western blotting, respectively. Results：Compared with the blank control group, the phosphorylated ERK1/2, JNK, and p38 protein levels were significantly increased (P<0.05), and the mRNA and protein expression of FOXA2, E-cadherin, CD44 and ZO-1 were significantly decreased (P<0.05) when cells were treated with CSE. CSE treatment with ERK, JNK or p38 inhibitors significantly improved the expression of the above genes and proteins (P<0.05). Conclusions：Smoking can affect the differentiation of bronchial epithelial cells, and the MAPK/FOXA2 signaling pathway plays an important regulatory role in this process.