To investigate the possibility of development as a whitening agent using pomegranate (Punica granatum L., Punicaceae) leaf extracts, we measured 1-diphenyl-2-picryl hydroazyl (DPPH) assay, nitroblue tetrazolium/xanthine oxidase (NBT/XO) assay, intracellular reactive oxygen species (ROS) scavenging assay, tyrosinase assay and melittin-induced intracellular Ca2+ mobilization and β-hexosaminidase release in B16 melanoma cells. Pomegranate leaf extracts had dose-dependently anti-oxidant activity in DPPH, NBT/XO and intracellular ROS assay. Pomegranate leaf extracts significantly inhibited purified tyrosinase activity using both substrates, L-3, 4-dihydroxy-L-phenylalanine (L-DOPA) and L-tyrosine. On the other hand, pomegranate leaf extracts significantly inhibited melittin-induced intracellular Ca2+ mobilization and β hexosaminidase release in B16 melanoma cells. Therefore, these results suggest that pomegranate leaf extracts may be useful for the development as whitening agents.