Human neutrophil elastase (HNE) exists in high concentrations in airway secretions and produces mucus hypersecretion in patients with chronic obstructive pulmonary disease (COPD). L-carbocisteine improves the quality of life and reduces exacerbation in COPD patients. However the precise mechanism is uncertain. We examined the effects of L-carbocisteine on HNE-induced mucus hypersecretion and on the production of reactive oxygen species (ROS) which is associated with mucin production induced by HNE. NCI-H292, a human lung mucoepidermoid carcinoma cell line, was treated with or without HNE and L-carbocisteine. MUC5AC mRNA expression and ROS production in the cells, and MUC5AC protein concentration in supernatants were measured. HNE increased MUC5AC mRNA expression and MUC5AC protein concentration in supernatants in the cells. L-carbocisteine reduces HNE-induced mRNA expression and protein secretion of MUC5AC. L-carbocisteine also reduced ROS production in the cells induced by HNE. Reduction of HNE-induced mucus secretion by L-carbocisteine in the pulmonary epithelial cells may partly relate to the reduction of ROS.