The dried roots of Sophora flavescens Aiton (SFA) has been used in traditional medicine for treatment of inflammation, gastrointestinal hemorrhage, diarrhea, and asthma. In the present study, we investigated the effect of SFA on the inflammatory allergic reaction using human mast cell-1 (HMC-1). SFA (200mg/kg) inhibited the mast cell-mediated passive cutaneous anaphylaxis reaction in vivo and the release of histamine from rat peritoneal mast cells by compound 48/80. In addition, the expression levels of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-alpha, IL-6, and IL-8 were also decreased by SFA treatment. In molecular mechanism level, this study showed that SFA inhibited the nuclear translocation of nuclear factor (NF) kappaB through inhibition of the phosphorylation and degradation of IkappaB-alpha, which is an inhibitor of NF kappaB. Moreover, SFA suppressed PMA plus A23187-induced phosphorylation of the mitogen-activated protein kinase p38 and c-jun N-terminal kinase. The inhibited induction of NF kappaB promoter by SFA was determined using luciferase activity. These results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.