Recently, we demonstrated that leucine-rich glioma inactivated 3 (LGI3) is expressed in human skin. However, the role of LGI3 on melanocytes still remains unknown. The present study showed that LGI3 could serve as a stimulator for melanogenesis without affecting cell viability and cell proliferation. To determine the effects of LGI3 on melanin synthesis, Mel-Ab cells were treated with recombinant LGI3, and the melanin content was measured. Interestingly, LGI3 promoted the melanin synthesis in Mel-Ab cells. Western blot analysis demonstrated that LGI3 induced Akt activation and glycogen synthase kinase 3GSK3phosphorylation. Moreover, upregulation of microphthalmia-associated transcription factor (MITF) and tyrosinase mRNA and protein expression was exhibited in Western blotting and RT-PCR. Our results suggest that LGI3 promotes melanogenesis through the upregulaion of MITF and tyrosinase expression.