Abstract： Objective: To investigate the mechanism underlying the protectiveeffects of α1adrenoceptor antagonistprazosin (PRA) on lipopolysacchride (LPS) induced rat hepatic injury.Methods:LPS (2 mg/kg,i.p.) or LPS+PRA (4 mg/kg,i.g.) was administrated to rats.Intracellular free Ca2+ concentration (〔Ca2+〕i) of liver tissue ,serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),lactate dehydrogenase(LDH),γglutamyltransferase(GGT) levels were measured six hours later, and liver histological examination were performed 24 hours later.The dynamic changes in secretory phospholipase A2 (sPLA2)、tumor necrosis factorα(TNFα)、prostag landin E２(PGE2) in serum were measured.Results:PRA significantly reduced the LPSinduced hepatocyte 〔Ca2+〕i concentration and serum levels of AST,ALT,LDH and GGT.Histological examination revealed that treatment with PRA could prevent the hepatocyte necrosis and inflammatory infiltration. In addition,PRA significantly decrease the secretory phospholipase A２(sPLA2) activity and the production of hepatocyte TNFα and PGE2 in serum induced by LPS.Conclusions:The protective effects of PRA on acute endotoxic hepatic injury may be mediated by attenuating hepatocyte Ca2+overloading and decreasing TNFα formation,subsequently resulting in inhibition of sPLA2 release and inflammatory mediators production.