The effect of aqueous extract of Terminalia chebula fruit (Combretaceae) (TCAE) by anal administration onmast cell-dependent immediate-type anaphylactic reactions was investigated. TCAE (0.005 to 1g/kg) inhibited systemic anaphylaxis induced by compound 48/80 in mice. When TCAE waspretreated at the same concentrations with systemic anaphylaxis, the plasma histamine levelswere reduced in a dose-dependent manner. TCAE (0.1 and 1 g/kg) also significantly inhibited localanaphylaxis activated by anti-DNP IgE. TCAE (0.001 to 1mg/ml) dose-dependently inhibited thehistamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. Moreover, TCAE (0.01 and 0.1mg/ml) had a significant inhibitory effect on anti-DNPIgE-mediated tumor necrosis factor-a (TNF-a) production from RPMC. These results provideevidence that anal therapy of TCAE may be beneficial in the treatment of systemic and local mastcell-dependent anaphylaxis.