Background: The aminoglycoside antibiotic gentamicin (GEN) was associated with nephrotoxicity in humans. Curcumin (CUR) supplementation is effective for preventing or ameliorating the renal toxicity of some drugs in patients and animals. Aim of Work: Investigating the possible protective role of Curcumin against the adverse gentamycin renal changes in rats and ellucidating its mechanism of action.Material and Methods: Twenty four adult male rats were used in this study. The animals were divided into four groups; Group I (control group), GEN group (II) received Gentamicin (100 mg/kg/day) for 21 days, CUR group (III) received Curcumin for 21 days, GEN + CUR group (IV) received GEN together with CUR (100 mg/kg) for 21 days. All animals were euthanized at the end of experiment and the kidney was obtained. Renal homogenates were assessed for oxidative stress markers Glutathione (GSH) and Malodialdehyde (MDA). Paraffin sections were processed then stained with Hx & E, Masson's trichrome and immunohistochemical stains: BAX (for apoptosis) and PCNA (for cell proliferation).Results: Curcumin had significantly (p