A novel technique for synthesis of monodisperse silica microparticles (MSMs), using spherical synechocystis sp. PCC 6803 as bio-templates, has been successfully developed. Various approaches including FESEM, TEM, FTIR and Small-angle X-ray scattering were used to characterize the intermediate and the final products. The results showed that MSMs retained the original morphology and uniformity of the PCC 6803 cells, and the average diameter of MSMs is almost the same with the cells. The possible mechanism for the formation of MSMs is proposed. With the surface modification by Sepharose CL-6B, the resultant MSMs were demonstrated as the good chromatography packings for protein separation. Therefore, this convenient, low cost and reproducible synthesis process may be used to prepare the MSMs with various sizes and shapes by the proper selection of original bio-templates. (C) 2013 Elsevier B.V. All rights reserved.