Recruitment of monocytes to endothelial cells is important during early stages of atherosclerosis development, which is activated in response to a number of inflammatory stimuli, including oxidized low-density lipoprotein (ox-LDL). Montelukast is a licensed drug approved by the Food and Drug Administration (FDA) and clinically used for the treatment of asthma by reducing the eosinophilic inflammation in the airway. Little information regarding the effects of Montelukast on endothelial inflammation has been reported before. In the current study, we found that Montelukast markedly reduced ox-LDL-induced monocyte adhesion to human umbilical vein endothelial cells. In addition, the inhibitory mechanism of Montelukast was associated with suppression of adhesion molecule expression, including VCAM-1 and E-selectin. Mechanistically, ERK5 mediated expression of the transcriptional factor KLF2 was found to be involved in the anti-inflammation effects of Montelukast against ox-LDL induced endothelial inflammation. Results indicate that Montelukast plays a protective role in the early stages of atherosclerosis. (C) 2017 Elsevier Inc. All rights reserved.