Photo-aging of skin is caused by chronic irradiation of Ultraviolet A (UVA). It has been known that chronic irradiation of UVA induces loss of dermal extracellular matrix due to loss of fibroblast cells and their versatile functions. Melanogenesis induced by alpha-melanocyte stimulating hormone (α-MSH) is a representative mechanism to protect skin against UV. However, there are few studies on another effect of α-MSH on protection of UVA. To demonstrate another function of α-MSH in fibroblasts, in this report, we present the alteration of transcription patterns by α-MSH in UVA-irradiated human dermal fibroblasts (HDFs). Eleven genes with known functions for proliferation and hormone secretion were significantly up-regulated and 31 transcripts for apoptosis were down-regulated by α-MSH. Especially, bax, one of well studied apoptosis related genes, was down-regulated by α- MSH in UVA-irradiated HDFs. Moreover, viability decreased by UVA was recovered by α-MSH. These results demonstrate that α-MSH is a critical repressor of UVA-dependent growth inhibition and apoptosis by regulating the expression of transcripts in HDFs.