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Histamine and leukotrienes (LTs), the chemical mediators released from mast cells, play an important role in type-I allergies such as hay fever. Echinacea purpurea(EP) has traditionally been used for herbal tea and has been reported to show biological functions. We evaluated the inhibitory activity of water extracts of EP petals, leaves, and stems against the chemical mediators released from mast cell lines. Petal and leaf extracts exhibited a significant inhibitory effect on histamine release from the stimulated cells, while the stem extract did not exert any effect. Activity of the petal extract was much stronger than that of the leaf extract. All the extracts significantly suppressed LTB4production in the stimulated cells and displayed similar activities. The petal extract decreased Syk phosphorylation and Ca2+influx associated with signal transduction in the stimulated cells. These results suggest that EP petal extract may have a relieving effect on allergic symptoms.Graphical AbstractPetal extract of Echinacea purpureasignificantly inhibited chemical mediators released from stimulated mast cells, in which the suppression of tyrosine phosphorylation and Ca2+influx were associated.