Background:　Harpagoside　(HAR)　is　an　active　component　of　Scrophularia　ningpoensis　(SN),　which　has　anti-inflammatory　and　anti-immune　effects.　SN　is　used　widely　in　China　to　treat　various　diseases.　Recently,　SN　has　been　used　as　a　traditional　Chinese　medicine　injection　and　used　clinically.　However,　allergic　responses　to　these　injections　are　frequently　reported.　Aim:　We　examined　whether　the　main　component　of　SN,　HAR,　is　associated　with　the　allergic　reaction　to　SN.　Methods:　This　study　assessed　the　effects　of　HAR　in　mice　and　mast　cell　activation　to　characterize　its　anaphylactic　effects　and　underlying　mechanisms.　Mice　hindpaw　swelling,　serum　allergy　factor　detection,　enzyme-linked　immunosorbent　assays,　and　degranulation　assays　were　performed　to　measure　allergic　mediators　both　in　vivo　and　in　vitro.　Results:　The　present　study　indicated　that　HAR　induced　paw　swelling,　interleukin-6,　inositol　triphosphate,　tumor　necrosis　factor-alpha,　and　histamine　increases　in　mice.　Our　in　vitro　data　also　showed　that　HAR　induced　beta-hexosaminidase,　inositol　triphosphate,　and　interleukin-6　release,　leading　to　mast　cell　degranulation.　In　contrast,　neither　C48/80　nor　HAR　induced　local　anaphylaxis　in　STOCK　Kit(W-sh)/HNihrJaeBsmJNju　mice.　Conclusions:　HAR　is　a　potential　sensitization　compound　in　SN,　and　these　results　provide　information　for　the　safe　clinical　use　of　SN.