Currently, nanobioceramics have received much attention due to their potentially high biological performance. In the present study, the interactions between proteins and two types of hydroxyapatite (HA) ceramic particles with distinct microstructures were studied in vitro. Protein adsorption on the microwave sintered and conventionally sintered HA ceramic particles (named as HAMS and HACS, respectively) were carried out in simulated body fluid (SBF) containing model proteins or rat serum and then subjected to protein quantitative evaluation, SDS-PAGE, and Western blotting analysis. The ceramic particles were characterized by nitrogen sorption, Hg penetration, zeta potential, and solubility analysis. It was found that HAMS with nanosized crystallites had greater specific surface area and pore volume and wider pore size distribution ranging from 0.02 to 2 μm than HACS. Although bovine serum albumin and lysozyme have different electrical properties in SBF, both the model proteins showed higher adsorption amounts per gram solid on HAMS than HACS, as could be ascribed to the contribution of the micropores structure of HAMS. Similarly, HAMS adsorbed more serum proteins per gram solid than HACS when incubating in rat serum, and here the surfaces of both particles were almost completely covered by serum proteins, leading to almost the same protein adsorption amounts per unit area solid of HAMS and HACS. SDS-PAGE patterns proved that HA ceramic particles had different binding capacities for different serum proteins and was not highly dependent on the concentrations of the competing protein components present in rat serum. Western blotting analysis confirmed the enhanced adsorption of fibronectin and vitronectin on HAMS, indicating that HAMS might have better bioactivity than HACS. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 516–523, 2012.