Abstract: The nephrotoxic effect of cyclophosphamide (CP) may involve inflammation. Dexamethasone (DEXA) is a glucocorticoid used for the treatment of inflammatory disorders. This study examined the protective potential of dexamethosane (DEXA) against CP-induced nephrotoxicity in albino rats. Thirty-six adult male albino rats divided in to six groups (n = 6) were used. Group I (Control) was treated with normal saline (0.2 mL day^–1) intraperitoneally (i.p.) for 24 h. Group 2 was treated with DEXA (1 mg/kg/day i.p.) for 24 h. Group 3 was treated with CP (150 mg/kg/day i.p.) for 24 h. Group 4 was pre-treated with DEXA (1 mg/kg/day) for 24 h before treatment with CP (150 mg/kg/day i.p.) for 24 h. Group 5 was co-treated with DEXA (1 mg/kg/day i.p.) and CP (150 mg/kg/day i.p.) ip for 24 h. Group 6 was treated with CP (150 mg/kg/day i.p.) for 24 h before posttreatment with DEXA (1 mg/kg/day i.p.) for 24 h. At the termination of treatments, the rats were euthanized and blood samples were assessed for serum renal function markers. Kidney samples were evaluated for histology, malondialdehyde and antioxidants (glutathione, catalase, superoxide dismutase and glutathione peroxidase). Treatment with CP produced significant (p<0.001) increases in serum uric acid, creatinine, urea and kidney malondialdehyde levels with significant (p<0.001) decreases in serum albumin, total protein and kidney antioxidants in relation to control. CP caused tubular necroses and increased Bowman’s space in the kidneys of treated rats. CP-induced nephrotoxicity was significantly abrogated by post-treatment (p<0.05), co-treatment (p<0.01) and pre-treatment (p<0.001) with DEXA when compared to CP. DEXA may be effective against nephrotoxicity caused by CP.