This　research　aimed　to　explore　the　effect　of　augmenter　of　liver　regeneration　(ALR)　in　acute　pancreatitis　(AP)　of　mice　and　the　underlying　mechanism.　Caerulein　were　given　to　mice　to　get　AP　models.　AP　mice　were　given　saline,　ALR　plasmids　or　negative　control　plasmids.　Then,　pancreas　tissues　were　fixed　and　stained　for　histological　examination.　The　levels　of　serum　amylase,　serum　lipase,　MPO,　HMGB1,　TNF-α,　IL-1β　as　well　as　MCP-1　were　detected　by　ELISA　assay.　The　mRNA　levels　of　TLR4,　p65,　IκBα,　iNOS,　COX-2　and　GAPDH　were　examined　by　RT-qPCR.　The　protein　levels　of　HMGB1,　TLR4,　MD2,　MyD88,　IκBα　and　GAPDH　were　detected　by　western　blotting.　ALR　decreased　serum　amylase　as　well　as　lipase　levels　and　alleviated　the　histopathological　alterations　of　the　pancreas　in　AP　mice.　ALR　decreased　the　MPO　activity　of　pancreas　in　AP　Mice.　ALR　decreased　the　HMGB1/TLR4　signaling　pathway　in　AP　Mice.　ALR　decreased　pancreas　IL-1β　and　MCP-1　in　AP　mice,　and　also　decreased　plasma　TNF-α　and　IL-1β　in　AP　mice.　ALR　attenuated　the　cerulein-caused　increase　in　p65　mRNA　and　protein　levels,　but　had　no　effects　on　mRNA　and　protein　levels　of　IκBα.　The　AP　mice　significantly　promoted　the　mRNA　levels　of　iNOS　and　COX-2　that　was　inhibited　by　ALR.　HNE　formation　was　also　increased　in　AP　mice,　but　it　was　decreased　by　ALR.　ALR　alleviates　acute　pancreatitis　by　inhibiting　HMGB1/TLR4/NF-κB　signaling　pathway.　It　is　promising　to　alleviate　the　syndromes　of　patients　with　acute　via　targeting　ALR.