Background:Renal ischemia reperfusion injury (IRI) is a risk for acute renal failure. It leads to inflammation , increases tissue endothelial nitric oxid synthase(eNOS) , induces oxidative stress and reduces antioxidant capacity of renal tissue which affects renal function. Nesfatin-1 pretreatment had renoprotective effects against renal IRI.It was demonstrated that nesfatin-1 possessed antioxidant and anti-inflamatory effects. In view of the reported efficacy of nesfatin-1 on renal IRI, this study was designed to investigate the effect and the mechanism of action of intraperitoneal (ip) injectionof nesfatin-1 on renal IRI in a rat model.Material and methods: This study was excuted on 4 groups: Group I (the control group): included normal sham-operated rats.Group II (the I/R group) : included IR-induced rats. Group III (nesfatin-1group) : Rats received Nesfatin-1 at dose of (10 µg/kg.ip) 30 min. before sham operation surgery was performed as in group I. Group IV (nesfatin-1+IRI group) : This group was subjected to injection of nesfatin-1( 10 µg/kg, i.p.) 30 min before ischemia reperfusion surgery was performed as in group III. Renal function tests were assessed and, tissue malondialdehyde (MDA) ,nitric oxid (NO), and super oxid dismutase(SOD) were measured. Also, eNOS was immunohistochemically determined. Results: Renal I/R induced marked renal dysfunction associated with significant increase in MDA and NO, while antioxidant enzymes such as SOD was significantly reduced. Nesfatin-1 pretreatment significantly normalized these parameter compared with I/R group while,eNOSexpression showed significant decrease. Conclusion: Nesfatin-1 protected the kidneys against renal I/R injury by antioxidant and anti-inflammatory action , however it is not related to microcircular compensation. Keyword: ischemia-reperfusion, Nesfatin-1 and oxidative sterss. Abbreviation: IRI; ischemia reperfusion injury, eNOS; endothelial nitric oxid synthase, ip; intraperitoneal, MDA; malondialdehyde , NO; nitric oxid , SOD; super oxid dismutase .