<p>Gentamicin (GM) is an aminoglycoside antibiotic widely used to treat gram-negative infections. Oxidative stress is known to play an important role in the nephrotoxicity of gentamicin. Therefore, the aim of this study was to investigate the possible protective effect of protocatechuic acid (PCA), which is believed to have antioxidant properties, on nephrotoxicity induced by gentamicin. For this purpose, 32 rats were randomly divided into four groups: control (oral physiological saline), PCA (20 mg/kg orally), GM (80 mg/kg/day/i.p.), GM+PCA (80 mg/kg/day/i.p. GM and 20 mg/kg PCA orally). The sampling period was eight days. Blood samples were collected for biochemical analysis and kidney samples for immunohistochemical and histopathological examination. Serum levels of urea, creatinine, Na, K and Cl were measured using an autoanalyzer, while analyses of malondialdehyde (MDA), advanced oxidation protein products (AOPP), gutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were analyzed by ELISA. While the values ​​of urea (p&lt;0.001), creatinine (p&lt;0.001), MDA (p&lt;0.05) and AOPP (p&lt;0.05) decreased in the GM+PCA group compared to the GM group, the values ​​of GSH (p&lt;0.05) and GPx activity (p&lt;0.05) increased. In conclusion, in GM-induced nephrotoxicity, PCA prevented lipid peroxidation and protein oxidation, increased GSH levels and GPx activity, and reduced tubular epithelial necrosis, glomerular atrophy, 8-OHdG and Kim-1 expression in renal cells, according to histopathological and immunohistochemical results. This study once again highlighted that PCA is a good antioxidant, and it can be said that PCA has a protective effect against nephrotoxicity caused by GM.</p>