Perilla frutescens var. acuta Kudo (PF) is a traditional Korean medicinal herb for allergic reactionregulation. In the present study, we investigated the effect of 30% ethanol extract powder of PF(EPPF) and rosmarinic acid (RA), the active compound of EPPF on various allergic reactionsusing in vivo and in vitro models. EPPF and RA significantly inhibited compound 48/48-inducedsystemic anaphylactic reaction and histamine release (P < 0.05). In addition, EPPF and RAsignificantly inhibited passive cutaneous anaphylaxis (PCA) in a dose-dependent manner (P <0.05). These effects were stronger than those of disodium cromoglycate, the reference drug tested.EPPF and RA also significantly inhibited production of inflammatory cytokines, tumor necrosisfactor (TNF)-α interleukin (IL)-6, and vascular endothelial growth factor on the PCA reaction andphorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cell line,HMC-1 cells (P < 0.05). Moreover, EPPF and RA showed an inhibitory effect on lipopolysaccharide (LPS)-induced IL-4 production from whole spleen cells. Finally, EPPF and RA significantly decreasedIL-4-dependent IgE production by LPS-stimulated whole spleen cells (P < 0.05). In conclusion,these results indicate that EPPF has potent anti-allergic activities.