The aim of the present study was to elucidate whether gallic acid could modulate the inflammatory allergic reaction and to study its mechanism of action Gallic acid inhibited compound 48/80- or immunoglobulin E (IgE)-induced histamine release from mast cells. The inhibitory effect of gallic acid on the histamine release was mediated by modulation of cAMP and intracellular calcium. Gallic acid decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated pro-inflammatory cytokine gene expression and production such as TNF-α and IL-6 in human mast cells, and the inhibitory effect of gallic acid was on dependent nuclear factor-κB and p38 mitogen-activated protein kinase. Our findings provide evidence that gallic acid inhibits mast cell-derived inflammatory allergic reaction by blocking histamine release and pro-inflammatory cytokine expression.