To further access honeybee (Apis mellifera L.) venom (BV) as a cosmetic ingredient and potential external treatment for topical use, we investigated its ability to inhibit tyrosinase activity and melanin biosynthesis on melanogenesis in B16F1 melanoma cells. We found that BV increased the cell viability in B16F1 melanoma cell and BV (0.01~1 ${mu}g/ml$) inhibited melanin synthesis in with 10 nM ${alpha}$-melanocyte-stimulating hormone (${alpha}$-MSH) for 48 h. In addition, we used reverse transcription-polymerase chain reaction and western blotting for me melanogenesis-related genes such as tyrosinase to examine the mechanisms underlying the inhibitory effects of BV on melanogensis. BV inhibited direct tyrosinase activity, which decreased melanin synthesis in ${alpha}$-MSH stimulated B16F1 melanoma cells. Thease findings suggest that BV induces the downregulation of melanogenesis by inhibiting tyrosinase activation.