Background: Cyclophosphamide (CP) is commonly used as anti-cancer drug which causes tissue toxicity by its reactive metabolites. Oxytocin (OT) is a peptide hormone secreted by the hypothalamic paraventricular and supraoptic nuclei. It modulates the immune and inflammatory processes. Objective: Investigating the effects of oxytocin on CP induced-acute renal toxicity in adult male albino rats. Materials and Methods: Seventy adult male albino rats were divided into 5 groups:  0 group served as normal control (20 rats were subdivided into A&B; 10 rats each), group I served as positive control (20 rats injected with single intraperitoneal dose of CP and were subdivided into A&B; 10 rats each), Group-II (10 rats treated with OT for 7 days before CP injection then sacrificed 24 hours later with 0-A and I-A groups), Group III (10 rats treated with OT after CP injection for 10 days then sacrificed with 0-B, I-B & IV groups), and Group IV(10 rats treated with OT for 7 days before and for 10 days after CP injection).  By the end of the experimental period, blood samples were collected to measure serum creatinine and urea. Both kidneys of each rat were dissected out carefully. The right kidney was used for measurement of malondialdehyde (MDA), glutathione (GSH) and tumor necrosis factor alpha (TNF-α), while the left kidney was preserved for histological examination. Results: Administration of oxytocin alleviated CP-induced renal toxicity as evident from the decreased levels of kidney toxicity markers (urea, creatinine, MDA and TNF-α) and elevation of GSH levels. No significant differences were found between the groups treated with OT. Administration of oxytocin caused a significant improvement in kidney histopathology with alleviation of tissue inflammation and tissue recovery especially in rats treated with OT pre- and post-CP injection. Conclusion: Oxytocin has a protective and therapeutic role from CP-induced renal toxicity by modulating levels of MAD, GSH and TNF-α.