empagliflozin is currently available for the management of type 2 diabetes mellitus and had a reno-protective effect. Cisplatin (CP) is used in the treatment of different types of cancers but severe complications occur include nephrotoxicity, ototoxicity, neurotoxicity and bone marrow suppression. Objective: investigating the effect of Empagliflozin on cisplatin-induced nephrotoxicity in adult male albino rats with detecting possible underlying mechanisms. Materials and methods: 32 adult male albino rats were used in this work and divided into 4 equal groups: Control group, cisplatin group, group treated with cisplatin and empagliflozin (10mg/Kg) and group treated with cisplatin and empagliflozin (25mg/Kg) by oral gavage for ten consecutive days and cisplatin (30 mg/kg, i.p.) on the seventh day of treatment. In addition to routine weight assessment, kidney tissue nerve growth factor (NGF-β) and oxidative stress parameters were measured. As part of a biochemical evaluation of serum urea, creatinine, uric acid, albumin, calcium, and glucose. Total antioxidant, superoxide dismutase, TNF-α and IL-6 were measured. Results: in our study, Cisplatin significantly reduced antioxidant indices (TAC, Reduced glutathione (RG) and superoxide dismutase (SOD), body weight, NGF-β, and also significantly increased the plasma concentration of inflammatory cytokines (plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), malondialdehyde, urea and creatinine. Histopathologically, CP caused a significant kidney damage compared with control. Prophylactic and therapeutic application of empagliflozin significantly reversed CP-induced changes in all the above renal parameters either by low or high doses (P ≤ 0.05). Conclusion: Empagliflozin significantly ameliorated CP-induced biochemical and histopathological changes in the kidney and may be promising renoprotective effect against cisplatin chemotherapy where it reduced oxidative stress and possess anti-inflammatory, antioxidant and anti-apoptotic action