In this study, the behavior of cells on the modified surface, and the correlation between the modified substrates and the response of cells is described. A close-packed layer of nano-sized silica beads was prepared on a coverslip, and the adhesion, proliferation, and migration of BALB/3T3 fibroblast cells on the silica layer was monitered. The 550 nm silica beads were synthesized by the hydrolysis and condensation reaction of tetraethylorthosilicate in basic solution. The amine groups were introduced onto the surfaces of silica particles by treatment with 3-aminopropyltrimethoxysilane. The close-packed layer of silica beads on the coverslip was obtained by the reaction of the amine-functionalized silica beads and the (3-triethoxysilyl)propylsuccinic anhydride treated coverslip. BALB/3T3 fibroblast cells were loaded on bare glass, APTMS coated glass, and silica bead coated glass with the same initial cell density, and the migration and proliferation of cells on the substrates was investigated. The cells were fixed and stained with antibodies in order to analyze the changes in the actin filaments and nuclei after culture on the different surfaces. The motility of cells on the silica bead coated glass was greater than that of the cells cultured on the control substrate. The growth rate of cells on the silica bead coated glass was slower than that of the control. Because the close-packed layer of silica beads gave an embossed surface, the adhesion of cells was very weak compared to the smooth surfaces. These results indicate that the adhesion of cells on the substrates is very important, and the actin filaments might play key roles in the migration and proliferation of cells. The nuclei of the cells were shrunk on the weakly adhered surfaces, and the S1 stage in which DNA is duplicated in the cell dividing processes might be retarded. As a result, the rate of proliferation of cells was decreased compared to the smooth surface of the control. In conclusion, the results described here are very important in the understanding of the interaction between implanted materials and biosystems.