Abstract: Objective　To investigate the effect of montelukast on the secretion of mucus protein in lipopolysaccharide (LPS) induced human bronchial epithelial cells. Methods　Primary human bronchial epithelial cells were isolated and identified in vitro. LPS (1μg/mL) was used to induce cell inflammatory response. Montelukast (50 μmol/L, 20μmol/L, 10μmol/L) was used as intervention. The concertration of mucin-5 subtype AC (MUC5AC) in cell supernatants was measured by ELISA. The expression levels of MUC5AC mRNA and protein were determined by RT-PCR and Western-blot. DCFH-DA fluorescent probe was used to detect reactive oxygen species (ROS). To further elucidate the mechanism, NF-κB (p65)、IκBα、ERK1/2 phosphorylation before and after montelukast intervention were determined by Western-blot. Results　Montelukast decreases the expression levels of MUC5AC mRNA and protein in a dose-dependent manner in LPS induced human bronchial epithelial cells. Meanwhile, monteluskast suppresses ROS generation and NF-κB (p65)、IκBα、ERK1/2 phosphorylation. Conclusions In response to LPS induced inflammation, montelukast decreases the expression level of MUC5AC in vitro, which may be related to NF-κB and ERK activation.