The three-ply-walled-based system for controlled delivery of diclofenac was developed. The preparation of three-ply-walled microcapsules is essentially based on the technique of multiple-emulsion formation polymer at the interface followed by rigidization of the wall on evaporation of solvent. The protective colloids with surface-active properties were selected for the present study, viz. acacia gelatin, polyvinyl alcohol and sodium alginate. Ethyl cellulose was taken as hydrophobic polymer. The acacia/ethylcellulose/acacia-based three-ply-walled microcapsule system was selected for further studies. The three-ply-walled microcapsule were subsequently coated with poloxamer 188. The non-ionic hydrophilic surfactant coating retards uptake into the reticuloendothelial system. The coated and uncoated microcapsules were characterized for in vitro and in vivo performance. The microcapsules were noted to provide sustained release of the contained diclofenac. The plasma level observed indicated that poloxamer coating results in prolonged release of the drug. Organ distribution demonstrated a different distribution pattern when compared with uncoated microcapsules.