Background/aim: Chronic renal disorder is becoming a major health problem worldwide. The purpose of the present study was to investigate alterations in the renal antioxidant system in rats induced by repeated exposure to chlorpyrifos (CPF) alone and in conjunction with fluoride. Materials and methods: Wistar rats were randomly allocated to seven groups, each consisting of six rats, and were subjected to different treatment regiments for 28 days. Results: Significant increases (P < 0.05) in plasma protein, blood urea nitrogen, and creatinine levels indicated alterations in renal functions on repeated exposure to CPF or fluoride; moreover, these changes were more pronounced in animals exposed to both toxicants concurrently. A significant increase (P < 0.05) in malondialdehyde levels and decreases in superoxide dismutase, catalase, and glutathione peroxidase activities in renal tissue were noted, indicating renal damage on exposure to CPF, fluoride, or the combination of those. Conclusion: Our observations suggested that the concurrent exposure to CPF and fluoride increased the extent of renal damage. These findings indicate that this damage is due to increased free radical formation and a reduced function of the antioxidant system in renal tissue. Thus, the application of CPF as an insecticide should be reduced in areas where the fluoride levels in ground waters are high in order to minimize renal damage in exposed populations.