Mesoporous silica spheres with controllable particle size were synthesized in mixed ethanol-water solvent. These materials possessed same pore size distribution and pore channel geometry. The amount of ibuprofen (IBU) adsorbed in mesoporous channels increased with the surface area of mesoporous silica spheres. Three kinds of release fluids, simulated intestinal fluid (SIF, pH=7.4), simulated body fluid (SBF, pH=7.4), and simulated gastric fluid (SGF, HCl aqueous solution, pH=1.2) were used to investigate drug release. The effects of particle size and dispersancy of mesoporous spheres on drug release rate were discussed in detail. It was found that larger or agglomerate mesoporous silica spheres could delay the drug release process, which could be attributed to pore-mouth amount and mesopore channel length of mesoporous spheres. Furthermore, to obtain a well controlled drug release system, hydrophobic trimethylsilyl (TMS) groups were functionalized on the surface of mesoporous silica spheres. The release of IBU from TMS-functionalized mesoporous spheres was obviously delayed with the increase of TMS content. (C) 2008 Elsevier B.V. All rights reserved.