Since rat organic cation transporter 1 (Oct1, Slc22a1) is expressed mainly in the liver and mediates drug transport, its activity may determine the hepatic handling of cationic drugs. Here, we studied the regulation mechanism of the expression of rat Oct1, focusing on the nuclear receptors. Various nuclear receptors are considered to regulate expressions of many genes for membrane transporters and enzymes that are involved in the drug absorption and disposition. Previously, we demonstrated that some ligands of nuclear receptors affected the transcriptional regulation of rat Oct1 when examined in the primary cultured rat hepatocytes. In the present study, dexamethasone, a ligand of glucocorticoid receptor, down-regulated the expression of rat Oct1. In addition, the transport activity of rat Oct1, evaluated by the uptake of substrates of rat Oct1, was decreased by treatment of dexamethasone in comparison with untreated rat hepatocytes, showing a good agreement with the change in mRNA level. In conclusion, these observations suggested that the expression of rat Oct1 gene and the apparent organic cation uptake activity of rat hepatocytes are down-regulated by dexamethasone presumably via a glucocorticoid receptor.