The potential anti-wrinkle effects of adipose tissue-derived mesenchymal stem cells (AdMSCs) have recently been reported. In the present study, we demonstrated a protective effect of AdMSCs in a UV irradiationinduced hairless mouse wrinkle model. Mice treated with AdMSCs showed improvements in skin erythema index, moisture capacity and transepidermal water loss. The AdMSC-treated mice showed reduced wrinkle area, as measured by gross observation and replica image analysis, and had a thinner epidermis and increased collagen and elastic fiber content, compared with the control group, as measured by histopathological examination. These results suggested that AdMSCs may be effective in the treatment of wrinkles. The activity of AdMSCs was further confirmed by the reduction in MMP-3 mRNA expression in the skin of the AdMSC treated animals, which suggests that AdMSCs can protect the collagen from degradation induced by UV irradiation. Further studies will investigate detailed mechanisms of action of AdMSCs, with particular focus on AdMSC-derived secretory factors.