In the present study, we investigated the inhibitory effect of a crude extract from Magnolia officinalis (MOE) on melanogenesis in both mouse B16 melanoma cells and zebrafish. Our results showed that MOE inhibited melanogenesis in either a-melanocyte stimulating hormone (a-MSH)- or 3-isobutyl-1-methylxanthin (IBMX)-stimulated B16 cells in a dose-dependent manner with an IC50 value of 9.3 µg/ml. In addition, MOE also inhibited cellular tyrosinase activity with an IC50 value of 13.4 µg/ml while no inhibitory activity was found by MOE against cell-free tyrosinase activity. Moreover, western blotting and real time reverse-transcription polymerase chain reaction (qRT-PCR) analyses, respectively confirmed that MOE downregulated levels of tyrosinase protein but not that of its mRNA in a-MSH-stimulated B16 cells. These results demonstrated that MOE inhibits melanogenesis of B16 cells by a pre-translational regulation on tyrosinase gene expression. On the other hand, when using zebrafish as a depigmenting assay system, MOE could inhibit both melanogenesis and tyrosinase activity in the in vivo model. From the present study, MOE was proven to be a good candidate as a skin-whitening agent for treatment of skin hyperpigmentation.