Introduction: Interstitial lung diseases are groups of chronic lung diseases characterized by inflammation and fibrosis.  Aim of work: The present study was performed to evaluate the possible protective effect of valsartan versus dexamethasone on cyclophosphamide-induced lung injury in adult male albino rat. Material and Methods: Thirty male albino Rats were divided into 6 groups; 5 rats each: group I (Control), group II (Cyclophosphamide), group III (Valsartan), group IV (Dexamethasone), group V (Dexamethasone & Cyclophosphamide), and group VI (Valsartan and Cyclophosphamide). Lung specimens were taken on the 6^th day of experiment. Specimens were subjected to histological (Hematoxylin and Eosin, Periodic Acid-Schiff, and Masson's trichrome) and immunohistochemical (Alpha smooth muscle actin, Clsuter of Differentiation 86, and inducible Nitric Oxide Synthase) studies. Also, morphometric studies and statistical analysis were done. Results: Features of acute lung injury appeared in group II as thickening of interalveolar septa, narrowing of alveoli, and cellular infiltrations. There were significant increases in the mean area percentage of collagen fibers, inducible Nitric Oxide Synthase and Alpha smooth muscle actin, besides significantly increased number of Periodic Acid-Schiff -positive goblet cells and alveolar macrophages in anti- Clsuter of Differentiation 86 immuostained sections, and thickness of interalveolar septa. Sections in group V and group VI demonstrated that lung tissue restored normal histological and immunohistochemical results, compared to group II. There was a significant decrease in mean area percentage of collagen fibers, inducible Nitric Oxide Synthase and Alpha smooth muscle actin, number of Periodic Acid-Schiff -positive goblet cells and alveolar macrophages in anti- Clsuter of Differentiation 86 immuostained sections, and thickness of interalveolar septa as compared to group II.  Conclusion: valsartan and dexamethasone possess protective effects against cyclophosphamide induced lung toxicity with the upper hand was to valsartan.