We investigated the effect of methyleugenol on anaphylaxis. Methyleugenol completely inhibited systemic anaphylaxis induced by compound 48/80 in mice. Methyleugenol also inhibited local anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. Moreover, methyleugenol dose-dependently inhibited histamine release in mast cells activated by compound 48/80 or anti-DNP IgE. Northern-blot analysis demonstrated that significantly reduced level of the mRNA of L-histidine decarboxylase (HDC) was expressed in mast cells treated with methyleugenol, compared to that without methyleugenol. We conclude that methyleugenol directly affect histamine release and HDC gene over-expression in mast cells.