Abstract: Objective To study the fine structure changes of liver and the level of cytokine in endotoxin tolerant rats received intraperitoneal injections of GalN/LPS.Methods Endotoxin tolerance(ET)model of SD rats was induced by five daily intraperitoneal injections of 011mg/kg LPS.Normal control rats received intraperitoneal injections of the same volume saline.Then the rats were injected with D-GalN 800 mg/Kg and LPS 8μg/rat.On the sixth day,liver tissue and blood were collected 24 hours after the injection of D-GalN/LPS.Liver histopathology and fine structure of each group were observed by HE staining and electron microscope.The level of TNF-αand IL-6 were estimated by ELISA and the concentrations of endotoxin were determined by tachypleus amebocyte lysate.Results GalN/LPS induced acute liver injury was attenuated significantly by LPS pretreatment.The plasma ALT,AST and TBiL activity were decreased remarkably by LPS pretreatment.The concentrations of endotoxin and the TNF-αand IL-6 level were evidently lower in ET group than those in the ALF group.Conclusion LPS pretreatment could induce endotoxin tolerance of rat,which made decreased releases of TNF α,IL-6 and endotoxin.The alleviation of GalN/LPSinduced acute liver injury in ET rats suggested that ET could be used to reduce severe liver injury.