Objectives The purpose of this study was to examine the pathway of anti-allergic effects of Cheonmaec-tang (CMT). Methods We examined the cell viability, $eta$-hexosaminidase release, pro-inflammatory cytokines secretion and mRNA expressions, nuclear factor-kappa B (NF-${kappa}B$) (p65) activation, inbibitor kappa B-alpha ($I{kappa}B-{alpha}$) degradation, and MAPKs activation in RBL-2H3 cells pre-treated by CMT of 2.0 mg/ml, 4.0 mg/ml separately. Results We observed that CMT reduced the secretion of $eta$-hexosaminidase, TNF-$alpha$, IL-4 and the expression of COX-2 mRNA in RBL-2H3 cells. Furthermore, CMT inhibited the levels of activation of NF-${kappa}B$ (p65) protein, ERK MAPK, and degradation of $I{kappa}B-{alpha}$ in RBL-2H3 cells. Conclusions These results show that CMT has an anti-histamine effect and inhibitory effect of NF-${kappa}B$ (p65) through regulation of $I{kappa}B-{alpha}$ degradation. These suggest that CMT could be used as an anti-allergic medicine.