Food derived antioxidants have a strong potential effect on the long term as chemo preventive agents in disease states involving oxidative stress. This study was done to evaluate the brain oxidative stress induced by streptozotocin (STZ) in rats with consequent changes in brain neurotransmitters and examined the potential protective role of quercetin (QCT) against the changes STZ induced. Forty male albino rats were used in this study and divided into four groups (10 rats in each group) as follow: Group I (control group) received a vehicle, group II (quercetin group) received daily intra peritoneal injection of QCT (15 mg/kg body weight/day), group III (diabetic group) diabetic rats received a vehicle, group IV (treated group) diabetic rats received a daily intra peritoneal injection of QCT (15 mg/kg body weight/day). After 8 weeks, blood, urine and brain tissues samples were collected. Oxidant/antioxidant parameters were determined included DNA damage by measuring urinary8-hydroxyguanosine (8-OHdG) by Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis using electrochemical detector. Brain neurotransmitters were estimated by RP-HPLC and UV detection. The current data appeared that, STZ effectively increased oxidative stress parameters along with disturbances in brain monoamines. Quercetin injection attenuated these elevation, thus a significant decreased was observed in oxidative stress parameters and brain neurotransmitters in treated group compared to diabetic one. We concluded that quercetin seems to be a highly promising agent in protecting the diabetic rats against oxidative damage and in preventing disturbances in brain monoamines due to STZ induced diabetes.