Both melamine and cyanuric acid have low toxicity, but together they may cause serious lesions to the kidney, via an unknown mechanism.In this study, mice were exposed to 2 mg/kg/day, 10 mg/kg/day or 50 mg/kg/day of a mixture of melamine and cyanuric acid for 13 weeks and then evaluated for general health,pathological changes to the kidneys, oxidative stress and energy parameters and hypoxia-inducible factor-1α (HIF-1 α) change in the kidneys.Crystals, proteinaceous casts and compensatory expansion were found in the distal tubules after exposure to the mixture, together with the increase in absolute and relative kidney weight, indicating that the mixture induced toxicity to the kidney.The activities of total antioxidant capacity (TAC) and superoxide dismutase (SOD) and the concentration of glutathione (GSH) decreased,while the concentrations of lipid peroxidation (MDA) and protein carbonyl groups (PC) increased after exposure to the mixture of melamine and cyanuric acid, demonstrating that the mixture of melamine and cyarmric acid caused imbalance of antioxidant and reactive oxygen species (ROS) and excessive ROS induced oxidant damage to lipid and proteins in kidneys.The activities of malate dehydrogenase (MDH) and succinate dehyrogenase (SDH) decreased, however, the activity of lactic dehydrogenase (LDH) and the concentration of HIF-1α increased after exposure to the mixture of melamine and cyanuric acid.Accordingly, it was concluded that the mixture of melamine and cyanuric acid induce a hypoxic state in the kidneys and that both oxidative stress and hypoxia contributed to the lesion of kidneys.