Background/Aims: It has been reported that GHRP-2, a potent ghrelin receptor agonist, has anti-inflammatory effect. We investigated whether this GH secretagogue attenuates liver injury in LPS treated rats. Methods: Wistar rats were divided in control and LPS-treated rats(1 mg/kg),and were injected i.p. with saline or GHRP-2 (100 μg/kg) at 17:00 h and at 08:00 h the following day. All animals were humanly killed 4 h after the last injection. Serum levels of aspartate and alanine transaminases were measured as an index of liver damage. Circulating nitrites/nitrates and hepatic IGF-I and TNF-α were evaluated as possible mediators of GHRP-2 actions. Results: LPS increased serum levels of transaminases and nitrites/nitrates. Moreover, LPS increased hepatic TNF-α and decreased hepatic IGF-I mRNAs. GHRP-2 administration attenuated LPS effects on transaminases, nitrites/nitrates, TNF-α and IGF-I “in vivo”. To elucidate whether GHRP-2 is able to modulate transaminases production directly on the liver, cocultures of hepatocytes and nonparenchymal cells were incubated with LPS (100ng/ml) and GHRP-2 (10-7M). GHRP-2 prevented endotoxin-induced increase in transaminases release as well as in TNF-α and IGF-I mRNAs and decreased nitrite/nitrate release from cocultures of hepatocytes and nonparechymal cells. Conclusions: These data suggest that GHRP-2 has a protective effect on the liver in LPS injected rats that seems to be mediated by IGF-I, TNF and NO.