<p>In this study, we explored the anti-allergic actions of 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acids (18α-GA and 18β-GA), to compare the pharmacological properties of these stereoisomers and to clarify the immunopharmacological contribution of 18α-glycyrrhizin in licorice. 18β-GA exhibited anti-allergic effects in murine models of contact dermatitis and IgE-mediated immediate allergic dermatitis, whereas 18α-GA showed no such effects. To elucidate the mechanism underlying this variation, the blood concentrations of 18α-GA and 18β-GA were measured after the oral administration of both compounds; we detected only 18β-GA in sera. We also demonstrated that considerable amounts of 18α-GA remained in the small intestine, which indicates low absorption of 18α-GA from the gastrointestinal tract. In addition, 18α-GA, like 18β-GA, directly suppressed IgE-mediated degranulation in RBL-2H3, and both showed equivalent clearance after intravenous administration. In conclusion, 18α-GA was not absorbed through the gastrointestinal tract in mice and did not exhibit the anti-allergic actions exhibited by 18β-GA. To clarify the differences in absorbability between these two compounds further research focusing on the gastrointestinal absorption of 18β-GA is needed.</p> Graphical abstract <p></p>