Abstract: Thiolated-chitosan microspheres(Thio-Cs-Ms)loading quercetin(QT)as model drug were prepared. The thiol group content, drug-loading capability, morphology in SEM and in microscope before and after hydration, release in vitro and pharmacokinetics in rats were evaluated. The thiol group content was(147. 0±8. 2)μmol/g, the drug-loading capability was(5. 33±0. 12)%. There were several pores on the surface of microspheres observed in SEM images. The microspheres expanded to be sphericity immediately after hydrating, and their morphology were intact after release in microscope. The behavior of release in vitro were no significant difference in water, simulated gastric fluid and simulated intestinal fluid evaluated by dissolution curve similarity factor. The release of Thio-Cs-Ms was fit for Higuchi equation Q=0. 161t1/2. Thio-Cs-Ms exhibited enhancing muco-adhesive ability in excised stomach and intestinal experiments. The bioavailability of Thio-Cs-Ms was obviously higher than that of suspension and Cs-Ms loading quercetin after oral administration in rats. Thio-Cs-Ms loading quercetin might to be one of the most promising preparations of quercetin.