A water extract of licorice root inhibits granuloma angiogenesis in adjuvant-induced chronic inflammation (Phytother. Res., 5, 195, 1991). The present study has investigated the effects of licorice-derived compounds on granuloma angiogenesis. Isoliquiritin (0.31-3.1mg/kg), a licorice-derived flavonoid, inhibited the carmine content of granuloma tissue 50-fold greater than licorice extract. Glycyrrhizin (20-80mg/kg), a licorice-derived saponin, inhibited carmine content with a weak potency. The licorice extract (0.01-1mg/ml) also inhibited tube formation from vascular endothelial cells in a concentration-dependent manner. From the chemical structure-activities of used licorice-derived flavonoids (0.1-100μM), their potencies for anti-tube formation were in the order isoliquiritigenin>isoliquiritin>liquiritigenin»isoliquiritin-apioside. Glycyrrhizin (0.1-100μM) and glycyrrhetinic acid (0.1-10μM) increased tube formation. A glycyrrhizin (82μg/ml)-induced increase in tube formation was inhibited by isoliquiritin. The combined effect of a mixture of 82μg/ml glycyrrhizin and 4.2μg/ml isoliquiritin, a similar concentration ratio to their yield ratio in the licorice extract, corresponded to the effect of 100μg/ml extract. In conclusion, the anti-angiogenic effect of licorice extract depended on the anti-tube formation effect of isoliquiritin.