This research was initiated to reveal the beneficial properties of magnetized water (MW), alone or in combination with the angiotensin-converting enzyme inhibitor, Lisinopril, (Lis) on methotrexate (MTX)-induced AKI in rats, and to track the mechanisms involved in this impact. The results showed that the treatment with MW and Lis, either separately or in combination, brought about a significant reduction in serum urea and creatinine levels that were elevated upon administration with MTX. Both of MW and Lis inhibited the oxidative stress burden caused by MTX as indicated by lowering nitric oxide levels and up-regulating the total antioxidant capacity. Furthermore, both treatments decreased the increased levels of serum NAG, MIP-2 and KIM-1, which were enhanced due to MTX administration. Immunohistochemical examination of kidney tissue of both of MW- and Lis-treated groups reveal moderate and mild immune reactions for Cas-3, TNF-α, TGF-β and Bax, respectively, while the combined treatment resulted in negative immune reaction. The biochemical and immunohistochemical findings were confirmed by the histopathological investigation where both of MW and Lis exhibited moderate ameliorative effects on kidney tissue while the co-treatment produced marked improvement in the histological feature of kidney tissue. In conclusion, the co-administration of MW and Lis can synergistically attenuate the MTX-induced renal injury. Drinking MW as an adjuvant agent with Lis during the treatment of AKI can enhance the efficiency of this drug. This could be attributed to the advantage of MW as an antioxidant, anti-inflammatory and anti-apoptotic candidate.