BACKGROUND: Among the several disorders induced by sepsis, acute kidney injury (AKI) represents the most important economic burden problem that is associated with high mortality and morbidity rates. The aim of this study was to investigate the anti-inflammatory effects of ghrelin in sepsis-induced AKI and the possible role of vagus nerve. METHODS: Five groups were included: sham, cecal ligation and puncture (CLP), CLP-ghrelin, CLP-vagotomy and CLP-vagotomy-ghrelin group. RESULTS: Ghrelin treatment immediately after induction of CLP, significantly improved renal Glomerular filtration rate (GFR), serum creatinine, BUN and renal necrosis score as compared to the unprotected CLP group. In addition, ghrelin significantly decreased renal TNF alpha (111.5 ± 10.35 vs. 291.8 ± 15.8 pg/mg ptn), VCAM1 (6.28 ± 1.7 vs. 12.9 ± 1.2 µ/g ptn) and MPO (0.95 ± 0.13 vs. 2.5 ± 0.4 µ/g ptn) without significant increase in renal IL-10. Those effects were abolished by vagotomy. CONCLUSION: We concluded that ghrelin could represent new therapeutic window in early treatment of sepsis-induced AKI and this could be mainly due to its anti-inflammatory effects.