Introduction: low-dos naltrexone has been discovered to be a potential therapy for multiple inflammatory conditions. Aim of the Work: This work was performed to demonstrate the inflammatory changes on the lung of adult albino rats sensitized with 2, 4 toluene diisocyanate and to assess the possible immunomodulator role of low dose naltrexone supplementation against these changes. Materials and Methods: This study was carried out on 40 adult albino rats for 4 weeks treated 7 days / week. The rats were divided into 4 groups each of 10 rats; Group I (negative control), Group II (positive control): each rat was gavaged orally with naltrexone same dose in group IV,Group III (2,4 toluene diisocyanate): each rat was sensitized intranasally with 5 μL of 10%of 2,4 Toluene Diisocyanate once daily then provoked with 5% 2,4 Toluene Diisocyanate and Group IV (2,4 Toluene Diisocyanate +Naltrexone): each rat was gavaged orally with 10 mg/kg naltrexone after exposure to 2,4 Toluene Diisocyanate in the previous manner. Results: There was a significant increase in the means of the counts of blood eosinophils and neutophils in group (III) compared with control group (I). Cytokines production in serum and spleen cell cultured in vitro were significantly increased in group (III) compared to control group (I). Upon supplementation with low dose naltrexone combined to sensitized rats there was a significant decrease in the means of counts of blood neutrophil and eosinophil, cytokines production in serum and spleen cultured cell compared with group (III). Microscopic examination of 2,4 Toluene Diisocyanate sensitized group of lung revealed prominent infiltration of airways with numerous eosinophils was observed, and goblet cells were seen in the epithelium of bronchi. Upon supplementation low dose naltrexone to 2,4 Toluene Diisocyanate sensitized rats showed an improvement of the airway and goblet cells were not seen in the epithelium of bronchi.Conclusion: 2,4 Toluene Diisocyanate induced inflammation and sensitization in the lung in rats and with administration of low dose naltrexone modulate the secretion of cytokines protecting lung tissues. Recommendation: It is recommended to increase public awareness regarding the health impact of 2,4 Toluene Diisocyanate and the protective role of low dose naltrexone as an immunomodulator.