Fibric acid-shaped drugs raise high-density lipoprotein (HDL) cholesterol by upregulating the HDL-related genes through activating peroxisome proliferater activated receptor (PPAR)-alpha. We investigated the effects of fibrates to induce expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and increase HDL biogenesis in hepatocytes. Fenofibrate, bezafibrate, gemfibrozil, and LY518674 were tested for HepG2 cells and primary-cultured mouse hepatocytes. All the compounds examined increased ABCA1 expression and HDL biogenesis dependent on PPARalpha in association with the liver X receptor alpha upregulation. While fenofibrate and LY518674 showed exclusive dependency on PPARalpha for these activities, bezafibrate and gemfibrozil exhibited dependency on PPARbeta/delta and PPARgamma as well. On the other hand, cholesterol-enrichment of HDL may involve PPARgamma for fenofibrate and bezafibrate, and PPARbeta/delta for the fibrates examined except for bezafibrate. We concluded that fibrates enhance expression of ABCA1 in hepatocytes to contribute to increase of the HDL biogenesis in a PPAR-dependent manner, whether exclusively or nonexclusively on PPARalpha.