We investigated the effect of aqueous extract of Rehmannia glutinosa steamed root (RGAE) on the allergic reactions in vivo and in vitro. RGAE dose-dependently inhibited systemic allergic reaction induced by compound 48/80. When RGAE was pre-treated at the same concentrations with systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. RGAE dose-dependently inhibited skin allergic reaction activated by anti-dinitrophenyl (DNP) IgE. RGAE also dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 or anti-DNP IgE. Moreover, RGAE had significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production of RPMC. These results indicate that RGAE may be beneficial in the regulation of immediate type allergic reaction.