1. Objectives The roots of Sophora flavescens Aiton (SFA) are widely used as a herbal remedy for allergic inflammation. In this study, we invested the effect of SFA on passive cutaneous anaphylaxis reaction and histamin releas and we demonstrated that SFA suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor-${alpha}$ (TNF-${alpha}$), interleukin- 6 (IL-6), and interleukin -8 (IL-8), through inhibition of the $NF{kappa}B$, JNK and p38 pathway in the human mast cell line, HMC-1. 2. Methods To accomplish this, we invested passive cutaneous anaphylaxis reaction and histamin release at an animal experiment. In addition, we investigated the effect of SFA on the production of inflammation-related cytokines in HMC-1 cells that were co-treated with PMA and A23187, which can induce production of pro-inflammatory cytokines. 3. Results and Conclusions SFA induced passive cutaneous anaphylaxis reaction and histamin releas and supressed the expression of TNF-${alpha}$, IL-6, and IL-8. In addition, the protein levels of TNF-${alpha}$ were also decreased by SFA treatment. Furthermore, SFA inhibited the nuclear translocation of nuclear factor $NF{kappa}B$ through inhibition of the phosphorylation and degradation of $I{kappa}B-{alpha}$, which is an inhibitor of $NF{kappa}B$. Moreover, SFA also inhibited induction of MAPKs (JNK, p38) and $NF{kappa}B$ promoter-mediated luciferase activity. Taken together, these results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.