Luteolin　is　a　flavonoid　found　in　many　fruits,　vegetables,　and　herbs.　The　antiinflammatory　effects　of　luteolin　have　been　reported.　In　this　study,　the　effect　of　luteolin　on　allergic　diseases　and　the　underlying　molecular　mechanism　were　investigated.　We　found　that　luteolin　inhibits　Fc　epsilon　RI　(Fc　epsilon　RI)-　and　Mas-related　G　protein-coupled　receptor　X2　(MRGPRX2)-mediated　mast　cells　(MCs)　activation,　including　degranulation　and　release　of　cytokines　in　vitro.　Moreover,　luteolin　reduces　the　degree　of　swelling　and　Evans　blue　exudation　of　mice　paw　in　a　dose-dependent　manner.　The　concentrations　of　histamine,　TNF-alpha,　MCP-1,　IL-8,　and　IL-13　in　mice　serum　are　also　decreased　by　luteolin　administration.　Our　study　reveals　that　luteolin　can　inhibit　Fc　epsilon　RI-　and　MRGPRX2-mediated　allergic　responses　in　vivo　and　in　vitro,　and　our　results　discover　luteolin　inhibited　mast　cells　mediated　anaphylactic　reaction　by　inhibiting　the　phosphorylation　level　of　PLC　gamma.