The main purpose of this study was to evaluate liposomes containing a bile salt, sodium deoxycholate (SDC), as oral drug delivery systems to enhance the oral bioavailability of the poorly water-soluble and poorly permeable drug, cyclosporine A (CyA). Liposomes composed of soybean phosphatidylcholine (SPC) and SDC were prepared by a thin-film dispersion method followed by homogenization. Several properties of the liposomes including particle size, polydispersity index and entrapment efficiency were characterized. The in vitro release of CyA from these liposomes was less than 5% at 12 h as measured by a dynamic dialysis method. The pharmacokinetic results in rats showed improved absorption of CyA in SPC/SDC liposomes as compared to CyA-loaded conventional SPC/cholesterol (Chol) liposomes and microemulsion-based Sandimmun Neoral®. The relative oral bioavailability of CyA-loaded SPC/SDC and SPC/Chol liposomes was 120.3% and 98.6%, respectively, with Sandimmun Neoral® as the reference. The enhanced bioavailability of CyA was likely due to facilitated absorption by the liposomes containing SDC rather than improved release rate.