The aim of the current study was to investigate the possible protective role of quercetin against monosodium glutamate (MSG) induced oxidative stress and inflammation on the brain hippocampus of adult male albino rats. Thirty adult male albino rats were equally divided into 5 groups; Group I (control), group II received1 ml/ kg/ day of 0.5% of Dimethyl sulfoxide (DMSO), group III received 50 mg of quercetin/ kg/ day, group IV received1.6 g/ kg/ day of MSG, group V received quercetin and after one hour, rats received MSG as previously mentioned. All treatments were given orally for 8 weeks. Then rats were anesthetized, sacrificed and specimens from the brain hippocampus were taken for biochemical and histological studies. MSG exposure showed deleterious effects on Y-maze discrimination learning and memory, significantly increased tissue malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), interleukin- 1 beta (IL-1β), tumor necrosis factor-α (TNF-α), glutamate level and acetyl cholinesterase (AChE) activity with significant depletions of catalase (CAT) activities and reduced glutathione (GSH) content. This was accompanied with alteration in the structure of the brain hippocampus. Co-administration of quercetin along with MSG ameliorated the above mentioned effects. The results of this study have shown that quercetin has protective effects against MSG-induced toxicity in rat brain hippocampus.