We investigated the effects of hot-water extract from the root bark of Morus alba (HEMA) on anaphylactic reactions. Using in vitro and in vivo experiments, we examined whether HEMA could inhibit compound 48/80-induced systemic anaphylactic shock and anti-chicken gamma globulin (CGG) IgE-mediated rat peritoneal mast cell activation. HEMA significantly inhibited systemic anaphylaxis induced by the compound 48/80 in mice. HEMA also significantly inhibited the passive cutaneous anaphylaxis activated by anti-CGG IgE. HEMA had no cytotoxicity on rat peritoneal mast cells (RPMC). Moreover, HEMA dose-dependently inhibited mast cell degranulation, histamine release and calcium uptake into RPMC induced by the compound 48/80 or anti-CGG IgE. When HEMA was added, the level of intracellular cAMP in RPMC showed a transient and significant increase (5-fold) compared with that of control cells. HEMA also inhibited significantly the compound 48/80-induced cAMP reduction in RPMC. These results suggested that HEMA inhibits the compound 48/80- or anti-CGG IgE-induced mast cell activation and its inhibitory effects on mast cell activations were favorably comparable to disodium cromoglycate. And HEMA is a candidate for effective therapeutic tools of allergic diseases.