We examined the inhibitory activities of various flavonoids, including the flavanones, flavones/isoflavones and flavonols, on collagenase from Clostridium histolyticum to establish their therapeutic potential against skin inflammation and photoaging. In general, the flavonols were stronger inhibitors than the flavones/isoflavones, and this indicated the importance of the C-3 hydroxyl substitution. Quercetin was the most active flavonoid among those tested, and it showed an IC50 of 286 microM. These novel results suggest that certain flavonoids, particularly the flavonols, may prevent collagen breakdown by inhibiting collagenase in inflamed skin as well as photoaged skin.