Baicalin and its aglycone, baicalein, being are strong antioxidants and have various pharmacological actions. Baicalein has shown a unique metabolic fate in rat intestine, being excreted into the intestinal lumen from mucosal (epithelial) cells following glucuronidation of baicalein absorbed after oral administration. The purpose of this study was to examine the absorption and excretion of baicalin and baicalein in a Caco-2 cell monolayer model to evaluate the disposition of baicalin and baicalein in the human intestine. When baicalein at 5μM was loaded on the apical side of the Caco-2 cell monolayer, baicalein was not transferred to the basolateral side, but more baicalin was excreted onto the apical side than was being absorbed onto the basolateral side. The amount of baicalin recovered on both sides accounted for more than 90% of the baicalein absorbed from the apical surface. This was supported by the fact that Caco-2 cell microsomes showed UDP-glucuronate glucuronosyl-transferase activity towards baicalein to form baicalin. On the other hand, when baicalein was loaded at higher concentrations, baicalin excretion became saturated, and then baicalein was transferred to the basolateral side. Furthermore, baicalin efflux was not inhibited by MDR1/P-glycoprotein substrates such as ciclosporin and vinblastine, but significantly inhibited by multidrug resistance-associated protein 2 (MRP2, ABCC2) substrates such as probenecid and genistein. MRP2 was also detected in Caco-2 cells by Western blotting using specific antibodies. In addition, baicalin, but not baicalein, enhanced dose-dependently the vanadate-sensitive ATPase activity of human MRP2. These results indicated that, in Caco-2 cells, any baicalein absorbed after loading at low concentrations of baicalein was not transferred to the basolateral side, but was first transformed into baicalin in the cells and excreted through the action of MRP2, mainly to the apical side.