Oral administration of the perilla leaf extract (PLE) to mice inhibits inflammation, allergic response, and tumor necrosis factor-α production. We also found that PLE suppressed the tumor necrosis factor-α (TNF-α) production in vitro. Using the inhibitory activity of TNF-α production in vitro as the index for isolation, we searched the active constituents from PLE and isolated luteolin, rosmarinic acid and caffeic acid as active components. Among the isolated compounds, only luteolin showed in vivo activity: inhibition of serum tumor necrosis factor-α production, inhibition of arachidonic acid-induced ear edema, inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ear edema and inhibition of oxazolone-induced allergic edema. These results suggest that luteolin is a genuinely active constituent which is accountable for the oral effects of perilla.