High　mobility　group　box　1　(HMGB1)　is　a　classic　damage-associated　molecular　pattern　that　has　an　important　role　in　the　pathological　inflammatory　response.　In　vitro　studies　have　demonstrated　that　the　Janus　kinase　2　(JAK2)/signal　transducer　and　activator　of　transcription　3　(STAT3)　signaling　pathway　is　involved　in　the　regulation　of　HMGB1　expression,　mediating　the　inflammatory　response.　Therefore,　the　purpose　of　the　present　study　was　to　evaluate　JAK2/STAT3　pathway　involvement　in　the　subarachnoid　hemorrhage　(SAH)-dependent　regulation　of　HMGB1,　using　an　in　vivo　rat　model.　A　SAH　model　was　established　by　endovascular　perforation.　Western　blotting,　immunohistochemistry　and　immunofluorescence　were　used　to　analyze　HMGB1　expression　after　SAH.　In　addition,　the　effects　of　AG490　after　SAH　on　JAK2/STAT3　phosphorylation,　HMGB1　expression　and　brain　damage　were　evaluated.　The　results　of　the　present　study　demonstrated　that　JAK2/STAT3　was　significantly　phosphorylated　(P＜0.05)　and　the　total　HMGB1　protein　level　was　significantly　increased　(P＜0.05)　after　SAH.　In　addition,　the　cytosolic　HMGB1　level　after　SAH　demonstrated　an　initial　increase　followed　by　a　decrease　to　the　control　level,　while　the　nuclear　HMGB1　level　after　SAH　demonstrated　the　opposite　trend,　with　an　initial　decrease　and　subsequent　increase.　AG490　administration　after　SAH　significantly　inhibited　JAK2/STAT3　phosphorylation　(P＜0.05),　suppressed　the　expression　and　translocation　of　HMGB1,　reduced　cortical　apoptosis,　brain　edema　and　neurological　deficits.　These　results　demonstrated　the　involvement　of　the　JAK2/STAT3　pathway　in　HMGB1　regulation　after　SAH.