Objective: Verify the effects of exercise on oxidative stress parameters in the brain of hyperphenylalaninemic rats. Methods: Sedentary (Sed) and exercise (Exe) rats groups were subdivided into saline (SAL) and PKU. PKU groups were induced hyperphenylalaninemia through administration of alpha-methylphenylalanine and phenylalanine for 17 days, while SAL groups received saline. Exe groups conducted 2-weeks of aerobic exercise lasting for 20 min per day. At the 18th day, the animals were killed and the brain was homogenized to determine tiobarbituric acid reactives substances (TBA-RS) content, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Results: PKU model caused an increase in TBA-RS and SOD, and reduces CAT and GPx. Exercise was able to prevent all changes seen in the PKU group, except for the SOD activity. Background: Phenylketonuria (PKU) is a rare genetic disease caused by a deficiency in phenylalanine hydroxilase activity, leading to an accumulation of phenylalanine (Phe). Clinically, patients present severe intellectual disability, whose pathophysiology is still uncertain. Objective: In the present work we investigated the levels of different cytokines in cerebral cortex of rats submitted to an experimental model of PKU.