The present study was conducted to investigate the anti-allergic reaction with Glycyrrhiza uralensis. We examined cell viability, β-hexosaminidase release, IL-4 and IL-13 mRNA expression from RBL-2H3 cell after pre-treatment with 0, 100, 250, 500, 1000μg/ml of Glycyrrhiza uralensis water extracts. Effects of Glycyrrhiza uralensis on the degranulation and pro-inflammatory cytokines (IL-4 and IL-13) expression were evaluated with β-hexosaminidase assay, and RT-PCR analysis. We observed that Glycyrrhiza uralensis concentrations from 100μg/ml to 1000μg/ml had no effect on cell survival. The release of β-hexosaminidase decreased significantly with all concentrations of Glycyrrhiza uralensis extracts. The expression of the IL-4 and IL-13 mRNA were decreased by Glycyrrhiza uralensis in dose-dependent manner. These results that Glycyrrhiza uralensis has an anti-histamin effects and controls IL-4, IL-13 secretion on allergic reaction.