Foot and mouth disease virus (FMDV) cause one of the major scourge of the livestock industry affecting cloven-hoofed animals, causing tremendous economic losses. Infection occurs mainly through mucosal route; thereby stressing the importance of mucosal vaccination as one of the first steps in prevention and control. This study described a potential mucosal vaccination system for immunoprophylaxis against the disease by adopting an experimental approach in microencapsulation of inactivated 146'S' whole virus and recombinant FMDV polyprotein expressed in E.coli along with CpG ODN as a co-adjuvant in a poly (DL-lactide-co-glycolide) delivery system. The formulation was found to be an effective mucosal as well as systemic adjuvant and an efficient antigen delivery system. This study observed the possibility of using this novel preparation to elicit appreciable level of protection against FMDV at the mucosal, humoral and cellular level.