Cyclophosphamide (CP)-induced lung toxicity is a remaining obstacle against the benefcial use of this chemotherapeutic agent. More considerations were given to the role of Alogliptin (ALO) in ameliorating CP-induced toxicities in many tissues. We designed this study to clarify the protective potential of ALO against CP-induced lung toxicity in rats. ALO was administered for 7 days. Single-dose CP was injected on the 2nd day (200 mg/kg: i.p.) to induce lung toxicity. Rats were divided into four groups: control, ALO-treated, CP-treated and ALO+CP-treated group. Leucocytic count, total proteins, LDH activity, TNF-α, and IL-6 were estimated in the bronchoalveolar lavage fuid (BALF). The oxidative/antioxidants (MDA, Nrf2, TAO and GSH), infammatory (NFκB), fbrotic (TGF-β1) and apoptotic (PI3K/Akt/FoxO1) markers in pulmonary homogenates were biochemically evaluated. Rat lung sections were examined histologically (light and electron microscopic examination) and immunohistochemically (for iNOS and CD68 positive alveolar macrophages). CP signifcantly increased oxidative stress, infammation, fbrosis, and apoptosis markers as well as deteriorated the histopathological pulmonary architecture. These hazardous efects were signifcantly ameliorated by ALO treatment. ALO protected against CP-induced lung toxicity by mitigating the oxidative, infammatory and fbrotic impacts making it a promising pharmacological therapy for mitigating CP-induced lung toxicity.