Objectives Solar ultraviolet (UV) radiation causes skin damage including increasing skin thickness, edema and flush. Scutellaria baicalensis roots have been traditionally used as a remedy for allergic inflammatory diseases in China and Japan. In this study, we examined the effects of four flavonoids isolated from these roots, namely 2',5,5',7-tetrahydroxy-6',8-dimethoxyflavone (1), skullcapflavone II (2), 2(S)-2',5,6',7-tetrahydroxyflavanone (3) and 2(R), 3(R)-2',3,5,6',7-pentahydroxyflavanone (4), on acute UVB irradiation-induced skin damage in hairless mice. Methods The four flavonoids were orally administered twice daily, at doses of 10 and 50 mg/kg, for 14 consecutive days. The UVB irradiation was performed at a dose of 200 mJ cm(-2) on days 7 and 8 after beginning oral administration of the four flavonoids. Key findings Compounds 1 and 4 prevented increases in skin thickness, levels of matrix metalloproteinases (MMP)-2 and MMP-9, and vascular endothelial growth factor (VEGF) induced by UVB irradiation. The other two flavonoids 2 and 3 had no effect. Conclusions Compounds 1 and 4 isolated from Scutellaria baicalensis roots may be useful for preventing skin inflammation induced by acute UVB irradiation.