UV-induced matrix metalloproteinases (MMPs) cause connective tissue damage and the skin to become wrinkled and aged. Here, we investigated the effect of 2 0 ,4 0 ,7-trihydroxyisoflavone (THF) on UV-induced MMP-1 expression in human skin fibroblasts (HSFs). We found that UV irradiation increases MMP-1 expression and that this is mediated by ERK and JNK activation, but not by p38 activation. Pretreatment of HSFs with 2 0 ,4 0 ,7-THF inhibited UV-induced MMP-1 expression in a dosedependent manner, and also inhibited the UV-induced activations of ERK and JNK by inhibiting MEK1 and SEK1 activation, respectively. Moreover, inhibitions of ERK and JNK by 2 0 ,4 0 ,7-THF resulted in the decrease of c-Fos expression and cJun phosphorylation/expression induced by UV, respectively, which led to the inhibition of UV-induced AP-1 DNA binding activity. This inhibitory effect of 2 0 ,4 0 ,7-THF on MMP-1 was not mediated by an antioxidant effect. In conclusion, our results demonstrate that 2 0 ,4 0 ,7-THF can inhibit UV-induced MMP-1 expression by inhibiting the MEK1/ERK/c-Fos and SEK1/ JNK/c-Jun pathways. Therefore, 2 0 ,4 0 ,7-THF is a potential agent for the prevention and treatment of skin aging.