Pentoxifylline (PX) is a highly water-soluble, hemorheologic drug that undergoes first-pass effect with 20 % bioavailability. Chitosan (CH), a biocompatible and biodegradable natural polymer, is used to increase drug bioavailability, as well as prolonging release. The aim of this study was to investigate the feasibility of enhancement of oral bioavailability of PX using CH. CH was used as an absorption enhancer for preparing the matrix tablet. The in vitro release and bioavailability of PX-CH tablet was compared with the reference product (Trental®-400, Sanofi-Aventis, Turkey). PX-CH tablets were prepared by the slugging method. The in vitro release studies were performed by a flow-through cell apparatus (USP Apparatus IV). A randomized, two-way crossover bioavailability study was conducted in 12 fasting, healthy male volunteers to compare PX-CH and reference tablets; both of them containing 400 mg PX. One tablet of either formulation was administered after a 12 h overnight fast. After dosing, serial blood samples were collected during a period of 12 hours. Plasma samples were analyzed for PX by a validated UV-HPLC method. The pharmacokinetic parameters AUC0-12, AUC0-inf, Cmax, tmax, λz, t1/2, Vd and CL were determined from plasma concentration-time profiles for both formulations. A higher in vitro release rate of PX was observed using acidic dissolution medium. The total in vitro release of PX was 104 % for PX-CH and 78.7 % for the reference after 12 hours. The mean maximum plasma concentration (Cmax) of PX-CH tablets was 1260±910 ng/mL after a tmax of 0.784±0.406 h. For the reference, they were 67.9±33.7 ng/mL and a tmax of 1.48±0.79 h, respectively. It was found that the relative bioavailability of PTX was significantly increased with CH, compared to reference. AUC0-inf values for test and reference were 1740±850 ng.h/ mL and 1270±780 ng.h/mL, respectively. Enhancement of the bioavailability of PX would suggest that CH could be used to improve oral bioavailability of PX.