Mast　cells　are　vital　mediators　of　drug　allergy　and,　therefore,　studying　the　relationship　between　drug　allergy　and　mast　cells　is　essential.　Sinomenine　is　the　principal　active　component　of　Sinomenium　acutum,　which　has　anti-inflammatory　and　anti-immune　effects,　and　is　used　to　treat　various　rheumatoid　diseases.　However,　allergic　responses　to　sinomenine　are　frequently　reported.　Therefore,　this　study　assessed　the　effects　of　sinomenine　on　mast　cell　activation　to　characterize　its　allergic　effects　and　the　underlying　mechanisms.　Enzyme-linked　immunosorbent　assay　(ELISA),　western　blot　analyses,　and　degranulation　assays　were　performed　to　measure　pro-inflammatory　and　allergic　mediators　in　P815　cells.　The　allergenic　effects　of　sinomenine　were　also　determined　in　mice　by　using　active　general　anaphylaxis　(ASA).　The　results　indicated　that　sinomenine　induced　inositol-1,4,5-trisphosphate　(IP＜sub＞3＜/sub＞)　production　and　the　release　of　histamine,　interleukin　(IL)-6,　and　endoplasmic　reticulum　Ca＜sup＞2+＜/sup＞　in　P815　cells.　Furthermore,　sinomenine　upregulated　the　phosphorylation　of　sarcoma　(Src),　phospholipase　C　(PLC)-γ1,　and　IP＜sub＞3＜/sub＞　receptor　(R).　Therefore,　sinomenine　induced　concentration-dependent　mast　cell　activation　directly　in　vitro　Furthermore,　our　in　vivo　data　identified　an　appropriate　intravenous　dose　that　did　not　induce　these　allergic　effects,　thereby　providing　information　for　the　potential　safe　clinical　use　of　sinomenine.