Introduction: Perfluorinated chemicals (PFCs) are materials that have many important industrial applications. Quercetin is a unique bioflavonoid that known with its antioxidant activity. Aim: To evaluate the histopathological effect of (PFOS) on rat renal cortex and the possible protective role of Quercetin. Materials and Methods: 45 adult male albino rats were divided into three groups, each contained 15 rats. The first group was the control group (I), which was splitted into three equal subgroups. The second group was (PFOS) receiving group (II) at a dose of 20mg /kg/day by gavage for 28 days. The third group was the protective group (III) which received the same dose of (PFOS) as group (II) in combination with Quercetin at a dose of 50 mg/kg b.w orally for 28 days. At the end of the study, the kidneys were dissected out and prepared for light microscopic examination. Results: The kidney sections of (PFOS) receiving group showed distortion of normal histology in the form of variations in the size and shape of renal glomeruli, peri glomerular inflammatory cell infiltrations, Disorganized renal tubules with dark stained (pyknotic) nuclei, cystic luminal dilatation and cytoplasmic vacuolations. In addition, some cortical convoluted tubules showed areas of interstitial hemorrhage, necrosis and exfoliation of tubular epithelial cells. Increased collagen fibers deposition and immune expression of PCNA and INOS stained sections. All these findings were improved by co-administration of Quercetin. Conclusion: Quercetin played an important role in improving the toxic effects of (PFOS) on kidney tissue of adult male rats. Introduction: Perfluorinated chemicals (PFCs) are materials that have many important industrial applications. Quercetin is a unique bioflavonoid that known with its antioxidant activity. Aim: To evaluate the histopathological effect of (PFOS) on rat renal cortex and the possible protective role of Quercetin. Materials and Methods: 45 adult male albino rats were divided into three groups, each contained 15 rats. The first group was the control group (I), which was splitted into three equal subgroups. The second group was (PFOS) receiving group (II) at a dose of 20mg /kg/day by gavage for 28 days. The third group was the protective group (III) which received the same dose of (PFOS) as group (II) in combination with Quercetin at a dose of 50 mg/kg b.w orally for 28 days. At the end of the study, the kidneys were dissected out and prepared for light microscopic examination. Results: The kidney sections of (PFOS) receiving group showed distortion of normal histology in the form of variations in the size and shape of renal glomeruli, peri glomerular inflammatory cell infiltrations, Disorganized renal tubules with dark stained (pyknotic) nuclei, cystic luminal dilatation and cytoplasmic vacuolations. In addition, some cortical convoluted tubules showed areas of interstitial hemorrhage, necrosis and exfoliation of tubular epithelial cells. Increased collagen fibers deposition and immune expression of PCNA and INOS stained sections. All these findings were improved by co-administration of Quercetin. Conclusion: Quercetin played an important role in improving the toxic effects of (PFOS) on kidney tissue of adult male rats.