Appetite is inhibited by the anorexigenic neuropeptides POMC (proopiomelanocortin) and CART (cocaine-amphetamine-regulated transcript) in the hypothalamus. The present study was performed to examine the inhibitory effects of baicalin against food intake and the upregulation of POMC/CART. Short-term food intake (48 h) was significantly inhibited by treatment with baicalin (10 mg/kg, p<0.05) in C57BL/6 mice. Immunohistochemical analysis showed that baicalin upregulated POMC and CART levels in the arcuate nucleus of the hypothalamus. These effects were also examined using an in vitro system. pPOMC-Luc or pCART-Luc plasmids were transformed into mouse N29-2 neuronal and human SH-SY5Y cells, and the activities of baicalin were examined in these cells. Baicalin increased POMC and CART promoter-driven luciferase activity in a dose-dependent manner without cytotoxic effects. These results suggest that baicalin downregulates short-term food intake while upregulating POMC and CART expression.