This study was conducted to investigate the effect of branch extracts of Vaccinium oldhamii (VOB) on melanin synthesis in B16F10 cells. VOB promoted melanin production in absence or presence of α-melanocyte-stimulating hormone (α-MSH) in B16F10 cells. However, VOB did not affect the expression of tyrosinase and TRP-1 associated with melanin synthesis at the mRNA and protein levels in B16F10. But, VOB decreased TRP-2 protein level and induced tyrosinase activation in B16F10 cells. Inhibition of tyrosinase activity and tyrosinase knockdown attenuated VOB-mediated melanin synthesis. In conclusion, VOB may stimulate melanin synthesis through activating tyrosinase activity.