Wound healing in a short period with minimum side effects is one of the major goals of modern medicinal sciences. Aim of the present study was to develop and evaluate the microsponge-based topical delivery system of Silymarin for sustained release and enhanced drug deposition in the skin for the treatment of wounds. Microsponge containing silymarin were prepared by quasi-emulsion solvent diffusion method. The effect of silymarin microsponges on human neonatal foreskin fibroblast proliferation rate was determined by MTT assay and was seen that the fibroblast proliferation rate increased with increase in concentration of silymarin. Formation of spherical and porous microsponges were confirmed by scanning electron microscopy and they were incorporated in the Carbopol 934 (1%) gel base and further evaluated by determination of pH, viscosity, spreadability etc. From in vitro drug release studies, silymarin microsponge loaded topical gel formulation has shown sustained release till 24 hrs whereas plain drug topical gel has shown an immediate burst release within 5 hours. From ex-vivo skin permeation studies, flux and permeability was found to be lowest for silymarin microsponge loaded topical gel formulation, indicating that with this kind of formulation systemic permeation of drug can be avoided. Therefore, Silymarin microsponge loaded topical gel prepared in this study is promising as being useful than conventional formulation in therapy for wound healing.