Adult male Sprague rats weighting (220 ± 30gm) were purchased from Faculty of Agriculture, Minia University Egypt. Experimen- AbstractCadmium (Cd) is a common environmental hazardous heavy metal. The standard treatment of heavy metal intoxication; chelators may have a minor role in Cd toxicity. Montelukast (ML) is an anti-inflammatory drug that is used mainly for managing asthmatic patients. Recent workers have tested ML for its antioxidant properties in various conditions and obtained encouraging results as regarding this effect. We investigated the protective and antioxidant effect of ML on pituitary gland, a highly sensitive organ to Cd toxicity. Four groups of rats were used and received distilled water, 10mg/kg ML, 3mg/kg Cd, and 10mg ML plus 3mg/kg Cd respectively. Antioxidant, histological, immunohistochemical and hormonal effects of Cd and ML were evaluated. The detrimental effect of Cd on pituitary gland was abolished by ML. The diminished hormonal effect of Cd was restored to normal levels. The increased MDA level and depleted oxidative enzymes on pituitary gland of rat exposed to Cd were restored by ML. lastly, histological and apoptotic effects of Cd were also, corrected significantly by ML. It is concluded that ML can protect against Cd-induced pituitary gland toxicity.