Abstract: Objective　 To investigate the effects and mechanism of tolvaptan on melanogenesis. Methods　 This study used B16F10 cells as a model. The effects of tolvaptan on cell viability and melanin content were evaluated through cell viability assays and melanin content quantification. The effect of tolvaptan on tyrosinase （TYR） activity was observed by tyrosinase activity detection. Western blot analysis was employed to investigate the impact of tolvaptan on the expression levels of TYR family proteins and other key proteins involved in melanogenesis. Results　Cell viability assays and melanin content quantification demonstrated that tolvaptan significantly reduced intracellular melanin levels without compromising cellular viability. Tyrosinase activity assays revealed no inhibitory effect of tolvaptan on TYR catalytic function. Western blot analysis indicated that tolvaptan downregulated the protein expression of TYR family members， microphthalmia-associated transcription factor （MITF）， cAMP-responsive element-binding protein （CREB）， and melanocortin 1 receptor （MC1R）. Conclusion　Tolvaptan can inhibit melanogenesis， and the molecular mechanism may be achieved through the MC1R/cAMP signaling pathway.

Key words: Tolvaptan, 　B16F10 cells, 　Melanin, 　cAMP, 　MC1R