Vitiligo is a skin depigmentation disorder with an increasing prevalence. Among recognized mechanisms is the oxidative stress that affects melanocytes which are responsible for skin pigmentation. Studies have shown that high concentration of hydrogen peroxide, or H2O2, induces apoptotic activities. Few studies have been done with lower doses of H2O2. Using human skin melanocytes, we investigated the effect of moderate concentration of H2O2 on melanocyte dendrites. Confocal data show that H2O2 at 250 µM induces loss of dendrites, as indicated by cytoskeletal proteins. ?-melanocyte stimulating hormone or ?-MSH pretreatment protects against H2O2-induced loss of dendrites, while ?-MSH alone enhances dendrites. PI3K/AKT inhibitor LY294002 and mTORC1 inhibitor Rapamycin inhibit ?-MSH-induced dendrites. In this study, we also investigated the effect of TNF? on cultured human skin melanocytes, since TNF? plays important roles in vitiligo. Confocal data demonstrate that TNF? induces NF?B activation. Western blot analysis shows that TNF? induces I?B phosphorylation and degradation. Interestingly, ?-MSH does not have any effect of TNF?-induced I?B degradation and NF-?B activation. ?-MSH, however, activates mTORC1 pathway. TNF? induces p38 but not AMPK? activation. Collectively, our data suggest that modulation of mTOR and NF-?B pathways may be a novel approach for better clinical management of vitiligo.