Flavonoids, abundant in plant food, interact with a number of efflux transporters, such as p-gp, which is expressed at the apical surface of epithelial cells of several organs. P-gp expression in the intestinal tract is suggested to limit the intrusion of xenobiotics into the organism. In vitro we studied the effects of 14 flavonoids on p-gp expression in human intestinal Caco-2 cells by Western blot, FACS analysis and RealTime-PCR. Cultivation of cells in media with flavonoids (10 mM) for four weeks increased p-gp protein expression at the mRNA and protein level up to 4,0 fold with the exception of apigenin and eriodictyol that did show any effect. Flavone fed daily to C57BL/6 mice at a dose of 400 mg/kg body weight over 6 weeks increased p-gp expression at the protein level in all intestinal segments. The effects of flavone on p-gp expression were most prominent in the segments with low initial expression (duodenum, jejunum) and lowest in the colon with high expression also in the control mice. In conclusion, our studies show that several flavonoids can increase p-gp expression by enhancing gene transcription and those effects could provide the basis of a reduced intestinal uptake of xenobiotics in vivo as a consequence of a diet rich in fruits and vegetables.