Abstract. Baicalein is one of the major flavonoids in Scutellaria baicalensis. However, the effects of baicalein on melanogenesis are unknown. The objective of this study was to evaluate the depigmenting capacity of baicalein and to elucidate its mechanism of action. B16F10 mouse melanoma cells were used to examine the effect of baicalein on melanogenesis by measurement of melanin content and tyrosinase activity after treatment. To ascertain the baicalein activity, the effect on two protein kinases, ERK and Akt and downstream microphthalmia-associated transcription factor (MITF) were examined by Western blotting and RT-PCR. Baicalein significantly inhibited melanin synthesis in a concentration-dependent manner without cytotoxicity. Tyrosinase activity was also reduced. Baicalein decreased MITF and tyrosinase levels but did not decrease MITF mRNA. Western blotting showed that baicalein induced ERK activation. Using the specific ERK phosphorylation inhibitor, PD98059, we blocked the hypopigmentation effect, and also abrogated the baicalein-mediated activation of ERK. However, baicalein did not induce Akt activation. These results suggest that the ERK pathway is involved in the melanogenic signaling cascade, and that ERK activation by baicalein reduces melanin synthesis via MITF downregulation and is subsequent to the inhibition of tyrosinase synthesis.