Wnt signaling plays a role in differentiation as well as development of human melanocytes. Using microarray analysis, hyperpigmentary skin of melasma expressed high levels of Wnt inhibitory factor-1 (WIF-1) compared to perilesional normal skin. In this study, the expression and functional role of WIF-1 on melanocytes were investigated. WIF-1 was expressed in both melanocytes of normal human skin and melanocytes in culture. The up-regulation of WIF-1 on cultured normal human melanocytes significantly induced the expressions of MITF and tyrosinase which was associated with increased melanin content and tyrosinase activity. Consistent with the stimulatory effect of WIF-1, WIF-1 siRNA reduced melanogenesis of the cells. Moreover, the treatment of WIF-1 on ex vivo cultured skin showed the increased pigmentation of the epidermis. These findings suggested that melanocytes express WIF-1 constitutively in vivo and in vitro and WIF-1 promotes the melanogenesis in normal human melanocytes.