The aqueous extract of Siegesbeckia pubescens (SPAE) inhibited compound 48/80-induced systemic anaphylaxis 100% with the dose of 1.0, 0.5 mg/g body weight (BW) at 1 h before or 5 min, 10 min after intraperitoneal injection of compound 48/80. The passive cutaneous anaphylaxis (PCA) reaction also inhibited to 78.5% by oral administration of SPAE(1.0 mg/g BW). When SPAE pretreated on mice at concentrations ranging from 0.0001 to 1.0 mg/g BW, the serum histamine levels were reduced in a dose-dependent manner. Moreover, SPAE ($100-800{mu}g/ml) dose-dependently inhibited the histamine release from peritoneal mast cells (RPMC) by compound 48/80 $(5{mu}g/ml)$. Analysis by microscopic appearance observation revealed that SPAE <TEX>$(500{mu}g/ml) stabilized the RPMC membrane. Therefore, these findings indicate that SPAE inhibits anaphylactic reactions through stabilization of mast cell membrane.