Poly(pyrrole) inverse opals (PPY-IO) with three-dimentional (3D) network of macropores were prepared by electropolymerization of pyrrole in the voids of polystyrene (PS) colloidal crystals and subsequently removing the PS. The as-prepared PPY-IO were then served as templates to be filled with prehydrolyzed silica sols followed by calcination to synthesize mesoporous silica spheres with well-controlled diameters. It was demonstrated that the reactant composition of the silica sol played an important role in controlling the shell thickness of the hollow spheres. Solid mesoporous silica spheres could be obtained when a concentrated TEOS sol was used. The morphology and pore structures of PPY-IO and silica spheres were characterized by SEM. TEM and small-angle XRD confirmed the ordered mesostructure of the prepared silica spheres with an average pore size of ca. 6 nm.