Recently, it has been found that Asiasari radix showed a hypopigmenting effect on melanogenesis through activation of mitogen-activated protein kinase (MEK)/extracellular signal-activated kinase (ERK) in B16F10 melanoma cells. However, the hypopigmenting effect of A. radix on the $alpha$-melanocyte stimulating hormone ($alpha$-MSH)-stimulated melanogenesis has remained unknown. The purpose of this study was to investigate the inhibitory mechanism of the partially purified A. radix (PPAR)-induced hypopigmentating effects on $alpha$-MSH-stimulated melanogenesis in B16F10 mouse melanoma cells. PPAR strongly inhibited tyrosinase activity and leads to decreased melanin synthesis in $alpha$-MSH-stimulated B16F10 melanoma cells. PPAR also decreased the $alpha$-MSH-induced over-expression of the melanogenic enzymes, tyrosinase, tyrosinase-related protein (TRP)-1, dopachrome tautomerase (Dct) and microphthalmia-associated transcription factor (MITF). We further showed that PPAR inhibits $alpha$-MSH-induced melanogenesis via phosphorylation of MEK/ERK and PI3K/Akt, and that their activation was blocked by MEK inhibitors, PD98059 and PI3K inhibitors, LY294002 in $alpha$-MSH-stimulated B16F10 melanoma cells. These results suggest that PPAR inhibits $alpha$-MSH-induced melanogenesis by activation of MEK/ERK and PI3K/Akt through MITF degradation, which may lead to down-regulation of tyrosinase.