The present study was investigated the effect of Houttuynia cordata THUNB water extract (HCWE) on mast cell-mediated anaphylactic reactions. The mast cell-mediated anaphylactic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. HCWE has been used as a traditional medicine in Korea and is known to have an antioxidant and anti-cancer activities. However, its speciﬁc effect of mast cell-mediated ana-phylactic reactions is still unknown. We examined whether HCWE could inhibit compound 48/80-induced sys-temic anaphylaxis, IgE-mediated passive cutaneous anaphylaxis (PCA), and mast cell activation. The oral ad-ministration of HCWE inhibited compound 48/80-induced systemic anaphylaxis in mice. HCWE also inhibited the local allergic reaction, PCA, activated by anti-dinitrophenyl (DNP) IgE antibody in rats. HCWE reduced the compound 48/80-induced mast cell degranulation and colchicine-induced deformation of rat peritoneal mast cells (RPMC). Moreover, HCWE dose-dependently inhibited histamine release and calcium uptake of RPMC in-duced by compound 48/80 or anti-DNP IgE. HCWE increased the level of intracellular cAMP and inhibited sig-niﬁcantly the compound 48/80-induced cAMP reduction in RPMC. These results suggest that HCWE may be beneﬁcial in the treatment of mast cell-mediated anaphylactic responses.