The immediate-type allergic reaction (anaphylaxis) is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. We investigated the effect of the gall of Rhus javanica (GRJ) on the model of the immediate-type allergic reaction, and studied its possible mechanisms. GRJ inhibited compound 48/80-induced systemic reactions in mice. GRJ attenuated immunoglobulin (Ig) E-mediated local allergic reactions. In addition, GRJ dose dependently decreased histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. The decreasing effect of GRJ on the histamine release was mediated by the modulation of cAMP and [Ca2+]i in mast cells. Furthermore, GRJ decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated TNF-alpha and IL-6 secretion in human mast cells. The inhibitory effect of GRJ on the pro-inflammatory cytokine was c-Jun N-terminal kinase and nuclear factor-kappaB dependent. Our findings provide evidence that GRJ inhibits mast cell-derived immediate-type allergic reactions, and suggest the possible mechanisms of action.