Aim of the study: The study was performed to investigate the role of Zamzam water (ZW) as an antioxidant against histological changes that occur in renal damage induced by n-hexane intoxication in rats by using the immunohistochemical technique. Method: The experiment was carried out at Environmental Toxicology Laboratory, Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt. A total of 20 male albino rats weighing 150-170g were obtained from the animal house of the Faculty of Medicine, Alexandria University. The rats were divided into four groups (5 rats in each cage). The Control group was fed a basal diet and given tap water (100ml/cage) daily for ten days. In group two the rats were given (n-hexane 300uL/kg .B.W) mixed with (0.5 ml) corn oil to each rat for the last five days of the experiment. In group three the rats were given (100ml/cage) of Zamzam water as drinking water daily for ten days. In Group four the rats were given (100ml/cage ) of Zamzam water for five days, after that given n-hexan 300uL/kg .B.W) mixed with (0.5 ml) corn oil last five days of experimental with continuous given Zamzam water. Kidney tissues of each rat were immediately removed and after weighted put into 10% neutral buffer formalin as a fixative solution. Ki-67 or P53 receptor subunits were examined in deparaffinized sections (5 µm) using an Avidin-Biotin-Peroxidase (ABC) immunohistochemical method. The results: The results observed a significant increase in the weight of the kidneys in the group treated with n-hexane compared with the control group, also a relative decrease in weight of the kidneys in the group co-treatment with Zamzam water and n-hexane. The detection and distribution of PCNA immunoreactivity (PCNA-ir) in the kidney sections in the different groups under study were observed. Faint positive reaction for PCNA-ir in the kidney sections in control and Zamzam water group, Strong positive reactions for PCNA-ir were detected in the n-Hexane group, while a moderate positive reaction for PCNA-ir in the kidney sections with pre-treatment Zamzam water revealed the normal structure of malpighian capsule and renal tubules with moderate degeneration of epithelial cell. Conclusions: Exposure to n-hexane showed a higher toxic effect with severe kidney damage and treatment with Zamzam water alone improved the antioxidant status of rats and could be useful as an antioxidant against environmental stress induced by toxic chemicals.