Background: Cyclophosphamide (CP) is a selective antibiotic used clinically as an anticancer drug. Treatment with CP exhibits a number of side effects. Here in this study, we explored the toxic effects of CP and the ameliorating effects of Sargassum cinereum in albino rats. Material and methods: Eighteen rats divided into 3 groups (6 rats each) control group, CP injected group in a dose of 200 mg/kg b. w and CP injected plus oral administration of S. cinereum group in a dose of 180 mg/kg b. w for 20 consecutive days. Results showed cyclophosphamides induced hematological, biochemical, oxidative and histological changes. Results: Hematological analyses revealed a significant decrease in the RBCs, WBCs' count and Hb concentration. Biochemical analyses revealed increase in the liver enzymes activityincluding ALT, AST and ALP, while albumin and total proteins were significantly decreased. Creatinine, urea, and uric acid levels as well as lipid profiles including cholesterol and triglycerides were increased signifcantly. Moreover, Oxidative stress was active that evidenced by a significant decrease in SOD, GSH and CAT levels, while a significant increase was recorded in the MDA level. For histopathology necrosis and inflammations were oserved in the hepatic and kidney tissues. Treatment with brown seaweed S.cinierium significantly ameliorated all of the above mentioned hematological, biochemical, oxidative damages and histopathological changes induced by CP injection. Conclusion: Cyclophosphamide induced its toxicity throught the activation of the oxidative system in the tissues, while the ameliorative effect of brown seweeds (S. cinereum ) achived throught activation the antioxidant system.