The neurological damages resulted by endosulfan poisoning is not completely elucidated, especially in cellular organelles such as mitochondria. In the present study, the pro-oxidant effect of endosulfan on brain mitochondria was first investigated. Gavages of endosulfan into rats at the dose of 2 mg/kg induced oxidative stress in this organelle since it provokes a significant reduction of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) level. In addition, a significant increase in mitochondria swelling and malondialdehyde (MDA) levels were observed in neuronal mitochondria, indicating clearly an intense peroxidation within mitochondria. Second, the protective effect of quercetin (QE) (10 mg/kg) against endosulfan-induced oxidative stress in mitochondria was also assessed. Indeed, the pretreatment of rats with QE protects brain mitochondria from oxidative stress, lipid peroxidation, and mitochondria swelling induced by endosulfan. The activities of antioxidant enzymes and the mitochondrial content of GSH and MDA were returned to control values. Thus, although endosulfan can have neurotoxic effects in brain rats, this toxicity can be prevented by quercetin.