We studied the inhibitory effect of the aqueous extract of Salvia plebeia (SPAE) on immediate hypersensitivity reactions. SPAE inhibited immediate hypersensitivity reaction induced by compound 48/80 in mice. When SPAE was employed in an immediate hypersensitivity reaction test, the plasma histamine levels were reduced in a dose-dependent manner. SPAE also inhibited the histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. The level of cAMP in RPMC, when SPAE was added, significantly increased compared with that of a normal control. These results indicate that SPAE may be beneficial in the treatment of immediate hypersensitivity reactions.