Abstract Background: Cyclophosphamide (CP) is used in the treatment of many types of cancers and immune disorders. Aim of Study: To support the role of queretin as antioxidant added to CP in the treatment of malignancies. Material and Methods: Twenty-five rats were divided into five groups; group I were injected intraperitoneally (i.p.) with normal saline, group II were injected with a single weekly dose of CP at 500mg/kg BW for one week, group III were injected with a single dose of CP at 500mg/kg BW for one week and treated with Quercetin (QUE) dissolved in corn oil at a dose of 100mg/kg BW daily via gastric tube for 7 days, group IV were injected with a weekly dose of CP at 500mg/kg BW for 3 weeks and group V were injected with a single dose of CP) at 500mg/kg BW for 3 weeks and treated with Quercetin (QUE) dissolved in corn oil at a dose of 100mg/kg BW daily via gastric tube for 21 days. All animals were sacrificed by decapitation 4-6 hours after their last medication intake. The extracted lungs were formalin fixed in 4% buffered formal-dehyde for morphological and immunohistochemical exami-nation. Results: CP was found to evoke histopathological altera-tions in the lungs via inducing oxidative stress and inflamma-tory reaction with improving effect by QUE. Conclusion: QUE could modulate CP induced pulmonary toxicity by its antioxidant effect.