AIM:To investigate the role of Kupffer cells(KCs)inacute hemorrhagic necrotizing pancreatitis-associatedlung injury(AHNP-LI).METHODS:Forty-two rats were allocated to fourgroups[sham operation,AHNP model,gadoliniumchloride(GdCl3)pretreatment,GdCl3control].In GdCl3pretreatment group,GdCl3was administered by caudalvein injection 24 h before the AHNP model induction.Blood from the iliac artery,alveolar macrophages andtissues from the pancreas and lung,were collected insix animals per group 3 and 6 h after acute pancreatitisinduction.TNF-α,IL-1 of serum,myeloperoxidase(MPO)of lung tissue,NF-kB activation of alveolar macrophageswere detected.Serum AST and ALT in sham operationgroup and GdCl3control group were tested.In addition,histopathological changes of the pancreas and lung wereobserved under light microscope.RESULTS:MPO of lung tissue and TNF-α,IL-1 levelsof serum were all reduced significantly in GdCl3pretreatment group compared to those in AHNP group(P<0.01).NF-kB activation of alveolar macrophageswas also attenuated significantly in GdCl3pretreatmentgroup compared to that in AHNP group(P<0.01).Thepathological injury of the lung was ameliorated obviouslyin GdCl3pretreatment group compared to that in AHNPgroup.Nevertheless,the serum amylase level did notreduce and injury of the pancreas was not prevented inGdCl3pretreatment group.CONCLUSION:Pulmonary injury induced by AHNPis mediated by KC activation and AHNP-LI can be significantly ameliorated by pretreatment with GdCl3andKCs play a vital role in AHNP-LI.