The effect of aqueous extract of Isodon japonicus Hara (Labiatae) (IJAE) on mast cell-mediated immediate-type allergic reactions was investigated. IJAE inhibited systemic allergic reaction induced by compound 48/80. When IJAE was pretreated at the same concentrations with systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. IJAE also inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE antibody. IJAE dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. IJAE inhibited the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells. In addition, the expression of TNF-alpha mRNA in HMC-1 cells was inhibited by IJAE. These results indicate that IJAE may be beneficial in the regulation of immediate-type allergic reaction.