Ethanol and aqueous extracts of Machilus thunbergii used traditionally for the treatments a wide variety of diseases were screened in vitro for the matrix metalloproteinase (MMP)-9 inhibitor actions. Meso-dihydroguaiaretic acid from the stems bark of Machilus thunbergii showed significant MMP-9 inhibition in human keratinocyte cells cause by ultraviolet irradiation. Here we investigated the effect of meso-dihydroguaiaretic acid, which was isolated from Machilus thunbergii, on UV-induced premature skin aging. We studied the effect of meso-dihydroguaiaretic acid on UV-induced MMP-9 expression in an immortalized human keratinocyte cell line, HaCaT, in vitro. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and meso-dihydroguaiaretic acid suppressed this UV-induced MMP-9 expression in a dose-dependent manner. Taken together, these results show that meso-dihydroguaiaretic acid can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that meso-dihydroguaiaretic acid should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging.