IgE-dependent mast cell activation is known to be associated with the allergic diseases. Pycnogenol (PYC) is a standardized extract of the bark of French maritime pine containing bioflavonoids with a potent antioxidant activity. The antiallergic activity of PYC was evaluated using both in vivo and in vitro experimental models. Oral administration of PYC significantly inhibited anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis in rats. In an in vitro study, PYC dose-dependently reduced histamine release from rat peritoneal mast cells (RPMC) triggered by anti-DNP IgE. PYC inhibited the protein expression and secretion of tumor necrosis factor-alpha and interleukin-6 in anti-DNP IgE-stimulated RPMC. Moreover, PYC decreased anti-DNP IgE-induced calcium uptake into RPMC. Furthermore, PYC suppressed nuclear factor-kappa B activation. From these results, the clinical use of PYC in the mast cell-mediated immediate-type allergic diseases is proposed.