Particle size development of monodispersed mesoporous silica spheres (MMSS) was investigated by laser scattering measurement, TEM and XRD in situ. Smaller particles suddenly appeared after the commencement of the experiment, then growing homogeneously to larger particles. It is assumed that residual silica precursors in solution preferentially reacted with existing particle surface silanol, preventing generation of new particles. This leads to the formation of monodispersed particles. Based on the mechanism, monodispersed mesoporous silica spheres with core/shell structure have been newly synthesized.