The carrier's surface biocompatibility plays a vital role in biochemical and biomedical fields. In this study, chitosan (CS) was used as a modified material to improve the surface biocompatibility of the microspheres. The particle size, size distribution and zeta potentials of these microspheres were measured before and after immobilized trypsin. Enzyme activity and zeta potential of immobilized trypsin were used to evaluate the immobilization. The experimental results showed that the enzyme activity of immobilized trypsin onto chitosan modified microspheres (CMMs) was higher than that onto no-chitosan modified microspheres (NCMs), even can approximately retain 80% of free trypsin. Meanwhile, electrostatic force was found to have the significance in the immobilization of trypsin. This work demonstrates that chitosan can improve the surface biocompatibility of carrier and provide a suitable surface for enzyme immobilization. Therefore, it is being used to its potential in preparation of the functional carriers required by high throughput screening of drugs (HTS) based on scintillation proximity assay (SPA) method. (C) 2012 Elsevier B.V. All rights reserved.