The aim of this study was to evaluate the pharmacokinetics of paclitaxel-loaded nanosponges (PLN) in rats. The study also evaluates the intrinsic effect of the dosage form on the improvement of paclitaxel oral bioavailability. Paclitaxel-loaded nanosponges were prepared and characterized in terms of size distribution, drug solubilization, and the kinetics of paclitaxel sedimentation. Taxol® and paclitaxel-loaded nanosponges were administered orally to rats. The plasma concentration of paclitaxel was determined using liquid chromatography. The average size of PLN was 350±25nm. The drug payload of paclitaxel was 500±0.27mg/g of lyophilized powder. The encapsulation efficiency was 99.1±1.0%, and 1.7±0.2% of paclitaxel was crystallized after 48h. The relative oral bioavailability of paclitaxel-loaded nanosponges was 256. After oral administration of paclitaxel-loaded PLN, the area under the plasma concentration time curve was significantly increased (∼ 3-fold) in comparison to the control group (p<0.05). The results indicated that PLN provided a promising new formulation to enhance the oral bioavailability of paclitaxel while avoiding the use of cremophore El: Ethanol in Taxol®. © 2010 Informa UK Ltd.