The objective of this study is to investigate the neuroprotective and antioxidant effects of subsequent pretreatment with Rutin as natural antioxidant on biomarkers of oxidative stress and inflammatory response in brain tissue induced by endotoxemia. This study was carried out on 42 male rats. The rats were divided into three groups. Group 1 (control) 12rats not receive drugs, Group 11 15 rats injected intraperiotneally (i.p) with a single dose of Lipopolysaccharide (LPS) at a dose 200 mk/kg. bwt, group III rats administered rutin orally at a dose 200 mg/kg b.wt/ day for three weeks and then injected (i.p) with a single dose of LPS at adose 200 mg/kg/B.w .Blood samples for serum seaparation and brain tissues were collected from all animal groups two times at one and three hours from the onest injection with endotoxin. All sera were subjected directly for determination of Tumor Necrosis Factor (TNF), Interleukin -6 (IL-6), Sialic acid (SA) and Nitric Oxide (NO). In addition determination of brain tissues of Glutathione peroxidase (GPX), Superoxide Dismutase (SOD), Catalase (CAT) and L-MDA. The obtained results revealed that, endotoxemia could potientially significantly increased serum TNF, IL-6 and brain l-MDA. Also induced a significant decrease in serum (SA), NO, and GPX, CAT, and SOD in brain tissues. Treatment with Rutin significant decrease in serum TNF, IL-6, and brain L-MDA. Also induced siginificat increase in serum (SA), NO, and GPX, SOD, and CAT in brain tissues from the obtained results it could be concluded Rutin may be protects against lipid peroxidation , oxidative stress and decrease the inflammatory response to endotoxin.