Background and Purpose Cysteinyl leukotrienes (CysLTs) are pro‐inflammatory lipid mediators that exacerbate disease state in several asthma phenotypes including asthma induced by allergen, virus and exercise. However, the role of CysLTs in irritant‐induced airway disease is not well characterized. The purpose of the current study was to investigate the effect of montelukast, a CysLT1 receptor antagonist, on parameters of irritant‐induced asthma induced by inhalation of chlorine in the mouse. Experimental Approach BALB/c mice were exposed to chlorine in air (100 ppm, for 5 min). Montelukast (3 mg·kg−1) or the vehicle (1% methylcellulose) was administered 24 and 1 h prior to chlorine exposure and 1 h prior to outcome measurements. Twenty‐four hours after exposure, responses to inhaled aerosolized methacholine, cell composition and an array of cytokines/chemokines in bronchoalveolar lavage (BAL) fluid were measured. Neutralizing antibodies against IL‐6 and VEGF were administered prior to exposures. Key Results Montelukast reduced chlorine ‐induced airway hyperresponsiveness (AHR) to methacholine in the peripheral lung compartment as estimated from dynamic elastance, but not in large conducting airways. Montelukast treatment attenuated chlorine‐induced macrophage influx, neutrophilia and eosinophilia in BAL fluid. Chlorine exposure increased VEGF, IL‐6, the chemokines KC and CCL3 in BAL fluid. Montelukast treatment prevented chlorine‐induced increases in VEGF and IL‐6. Anti‐IL‐6 antibody inhibited chlorine‐induced neutrophilia and reduced AHR. Conclusions and Implications Pre‐treatment with montelukast attenuated chlorine‐induced neutrophilia and AHR in mice. These effects are mediated, in part, via IL‐6.