Purpose Montelukast, a leukotriene receptor antagonist, is the most prescribed non-steroidal anti-inflammatory drug used as add-on therapy at later stages of asthma to prevent disease progression. Besides its direct anti-inflammatory effect due to blocking leukotriene action, montelukast has been proposed to have secondary anti-inflammatory and anti-fibrotic properties. This study aimed to investigate the modulatory effect of montelukast on the expression of major genes involved in airway inflammation (TNF, IL6) and remodeling (MMP9, TGFB1) in response to lipopolysaccharide (LPS) in vitro. Methods Effect of montelukast on LPS-induced acute inflammation was analyzed in the immortalized cell line derived from human bronchial epithelium, BEAS-2B. The expression of selected genes was measured by quantitative real-time polymerase chain reaction 0h and 24h after LPS stimulation in cells pretreated with montelukast. Results Montelukast was found to significantly attenuate increased TNF and IL6 gene expression, has a mild effect on MMP9, and has no effect on TGFB1 expression upon stimulation with LPS. Conclusion The results of our study indicate that that patients already using montelukast therapy would have adequate response to acute microorganism-induced inflammation. Additional anti-inflammatory effects of montelukast could be better exploited in clinical practice and modes of montelukast use should be reconsidered to improve the therapeutic approaches in asthma.