Introduction: Acute kidney injury (AKI) is a complex disorder occurring inmultiple settings and comprising several etiological factors. Ghrelin is a novel brain-gut peptide that plays various roles in mammals. It remains unknownwhether ghrelin plays a role in the management of AKI.Aim: To study the effect of ghrelin hormone on inflammatory induced renalinjury and if its effect is mediated through vagus nerve or not. Methods: The study was designed into two modules: Module A: (Ischemia for60 min and24h reperfusion injury), this module containing 40 rats divided into 5groups (8 rats /group). Group І: Sham operated for renal IRI, group ІІ: Renal IRI,group ІІІ: Renal IRI + ghrelin injection, group ІV: Renal IRI and subdiaphragmaticvagotomy and group V: Renal IRI + ghrelin injection + vagotomy.The second module B: Sepsis injury induced by cecal ligation and puncture(CLP): Another 40 rats were involved and divided into 5 groups (8 rats /group).Group VІ: Sham operated for CLP, group VІІ: CLP, group VІІІ: CLP+ghrelininjection, group ІX: CLP and subdiaphragmatic vagotomy, group X: CLP +vagotomy + ghrelin injection.At the end of the experimental period, systolic blood pressure was measured,24h urine was collected and body weight was measured for GFR determination.Blood samples were collected for assessment of BUN and plasma creatinine.Tissue samples from the kidney for histopathological examination and formeasuring the following parameters: TNF-α, IL-10, VCAM-1(vascular celladhesion molecule-1) gene expression and myeloperoxidase (MPO) activity in thekidney tissue.Results: There was a significant deterioration in the renal function in ischemicand septic groups. Ghrelin treatment immediately after induction of injury caused asignificant improvement in renal functions and decreasing inflammatory markersand leukocyte infiltration in the kidney tissue. However, vagotomy resulted in lossof the ghrelin's protective effect.