The aim of this study was to investigate the effect of ethanol extract of Fagopyrum esculentum on the melanogenesis. To determine whether ethanol extract of Fagopyrum esculentum suppress melanin synthesis in cellular level, B16F10 melanoma cells were cultured in the presence of different concentrations of Fagopyrum esculentum ethanol extract. In the present study, we examined the effects of Fagopyrum esculentum ethanol extract on cell proliferation, melanin contents, tyrosinase activity, expression of melanogenic enzyme proteins including tyrosinase, tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP-2). Cell proliferation was slightly increased by treatment with ethanol extract of Fagopyrum esculentum $(25-200 {mu}g/m{ell}).$ The ethanol extract of Fagopyrum esculentum effectively suppressed melanin contents at a dose of $100 {mu}g/m{ell}).$ It was observed that the color of cell pellets was totally whitened compared with the control. The ethanol extract of Fagopyrum esculentum inhibited tyrosinase activity, regulate melanin biosynthesis as the key enzyme in melanogenesis. Using western blot analysis, the ethanol extract of Fagopyrum esculentum dose-dependently decreased tyrosinase and TRP-1 protein levels, and tyrosinase and TRP-1 were detected in similar manner. ${alpha}-MSH$ leads to a stimulation of melanin synthesis through increase of tyrosinase activity, melanin contents and cytoplasmic dendricity. In this study, ethanol extract of Fagopyrum esculentum down-regulated the ${alpha}-MSH$-induced tyrosinase activity, melanin contents and cytoplasmic dendricity. Regarding protein levels of the melanogenic enzymes, the amounts of tyrosinase and TRP-1 was increased after incubation with a-MSH. The treatment of ethanol extract of Fagopyrum esculentum decreased the ${alpha}-MSH$-induced expression levels of tyrosinase and TRP-1. These results suggest that the ethanol extract of Fagopyrum esculentum exerts its depigmenting effects through the suppression of tyrosinase, TRP-1 and cytoplasmic dendricity. And it may be a potent depigmetation agent in hyperpigmentation condition.