The purpose of this work was to improve the oral bioavailability of poorly soluble drugs by incorporation into solid lipid nanoparticles (SLNs). All-trans retinoic acid (ATRA) was used as a poorly soluble model drug. Different formulations of SLNs loaded with ATRA were successfully prepared by a high-pressure homogenization method and using Compritol 888 ATO as lipid matrix. The particle size and distribution, drug loading capacity, drug entrapment efficiency (EE %), zeta potential, and long-term physical stability of the SLNs were investigated in detail. Drug release from two sorts of ATRA-SLN was studied and compared with the diffusion from ATRA solution in 0.1 M HCl, distilled water and phosphate buffer (pH 7.40), using a dialysis bag method. A pharmacokinetic study was conducted in male rats after oral administration of 8mgkg---1 ATRA in different formulations and it was found that the relative bioavailability of ATRA in SLNs was significantly increased compared with that of an ATRA solution. The amount of surfactant also had a marked effect on the oral absorption of ATRA with SLN formulations. Although an emulsion formulation also increased ATRA absorption, it was too unstable for use in clinical situations. The absorption mechanism of the SLN formulations was discussed. These results indicate that ATRA absorption is enhanced significantly by employing SLN formulations. SLNs offer a new approach to improve the oral bioavailability of poorly soluble drugs.