<p>Shark skin peptides, a kind of substance with a variety of biological activities, were shown to inhibit the activity of mushroom tyrosinase. This study was performed to clarify their inhibitory effects on melanin synthesis in B16F10 melanocytes and in vivo zebrafish models. In order to elucidate the inhibitory effects of shark skin peptides on B16F10 melanocytes, cell viability, morphologic changes, intracellular tyrosinase, and the melanogenesis-related proteins were determined. The results showed that the peptides were not cytotoxic to B16F10, and the morphology of the cells did not change significantly at the detected concentration. The intracellular melanin content and tyrosinase activity of B16F10 cells decreased in a concentration-dependent manner after the peptide treatment. The suppressive activity of the peptides on melanin synthesis is linked to the down-regulation of the important proteins involved in melanogenesis, such as tyrosinase, tyrosinase-related protein-1 (TRP1), and microphthalmia-associated transcription factor (MITF). The effects of shark skin peptides on melanin synthesis in zebrafish embryos showed that the peptides inhibit the production of melanin in embryos, and the melanin-related proteins were also detected as down-regulated. The results from ROS analysis suggested that the peptides are also capable of eliminating reactive oxygen species within the cells. In conclusion, the shark skin peptides could inhibit melanin synthesis, indicating that peptides may become additives for cosmetics potentially.</p>