The transport and metabolism of organic cationic endobiotics, nutrients and drugs are essential hepatic functions. Slc22A11 is the basolateral liver transporter mediating the uptake of organic cations, however, little is known about the regulation of this transport protein. PPAR- and PPAR- agonists are commonly used agents that regulate many hepatocellular transport functions. Thus, the purpose of this study is to examine the effects of PPAR agonists on the hepatic regulation and function of Slc22a11. Mice and H35 cells were administered PPAR- and PPAR- agonists and the effect on Slc22a11 gene expression was measured. We subsequently cloned the Slc22a11 promoter and employed chimeric constructs to assay Slc22a11 gene transcription. The effects of PPAR agonist treatment on organic cation uptake was also assayed. Slc22a11 expression was increased by PPAR- and PPAR- agonist treatment in both murine livers and H35 cells. Gene expression in H35 cells was further increased following transfection with expression vectors of PPAR transcription factors and PPAR agonist treatment. We cloned the promoter region of Slc22a11, identified a PPAR response element (PRE), and transfections with chimeric Slc22a11 promoter-reporter gene constructs demonstrate that the increased gene expression was transcriptionally regulated. Functional assays confirmed that cells treated with PPAR agonists displayed significant increases in organic cation uptake. PPAR- and PPAR- agonists transcriptionally increase Slc22a11 gene expression, and the increased Slc22a11 expression results in enhanced cellular organic cation uptake. These studies may have implication for the uptake of organic cationic drugs and for lipid metabolism.