BACKGROUND:?The? pathogenesis? and? progression? of? acute?liver? failure? (ALF)? are? closely? associated? with? intestinal?endotoxemia? because? of? the? high? permeability? of? the?intestinal? wall.? Treatment? with? ethyl? pyruvate? (EP)? has? been?shown? to? protect? liver? failure? effectively.? The? current? study?aimed? to? explore? the? relationship? between? proinflammatory?cytokines? and? intestinal? permeability,? and? to? investigate?whether? EP? administration? might? prevent? the? release? of?multiple? proinflammatory? cytokines? and? decrease? intestinal?permeability?and?therefore,?protect?the?liver?from?injury. METHODS:??The?ALF?model?was?induced?by?D-galactosamine?in? rats.? The? rats? were? randomly? divided? into? control? (saline,?i.p.),? model? (D-galactosamine,? 1.2? g/kg,? i.p.),? prevention? [EP?injection? (40? mg/kg)? 2? hours? ahead? of? D-galactosamine]? and?treatment?groups?(EP?injection?2?hours?after?D-galactosamine).?Samples?were?obtained?at?12?and?24?hours?after?ALF?induction,?respectively.? The? histology? of? liver? and? intestinal? tissue? was?accessed.? Serum? alanine? aminotransferase,? endotoxin,? D(-)-lactate,? diamine? oxidase? (DAO),? tumor? necrosis? factor-alpha?(TNF-α),? interferon-γ? (IFN-γ)? and? high? mobility? group? box-1?(HMGB1)?were?evaluated.?The?survival?of?rats?was?also?recorded. RESULTS:?The? rats? in? model? group? showed? severe? damage? to?liver? tissue? and? intestinal? mucosa? 12? and? 24? hours? after? ALF?induction.?EP?significantly?improved?liver?or?intestinal?injury.?In? addition,? serum? endotoxin,? D(-)-lactate,? DAO,? TNF-α,?IFN-γ? and? HMGB1? levels? were? significantly? increased? in? the?model? group? compared? with? the? control? group.? There? was?a? positive? correlation? between? intestinal? permeability? and?proinflammatory? cytokines.? EP? significantly? reduced? serum?endotoxin,?D(-)-lactate,?DAO,?TNF-α,?IFN-γ?and?HMGB1?levels.?The?median?survival?time?was?significantly?prolonged?in?both?prevention?and?treatment?groups?(126?and?120?hours?compared?with?54?hours?in?the?model?group). CONCLUSIONS:?EP?has?protective?and?therapeutic?effects?on?intestinal? mucosa.? EP? decreases? intestinal? permeability,? and?inhibits?the?release?of?multiple?proinflammatory?cytokines?in?rats?with?ALF.