Mucosal vaccination is one of the most effective methods to prevent infectious diseases because most pathogens enter the body at mucosal surfaces. Mucosal vaccination induces not only systemic immune responses but also mucosal responses compared to parenteral vaccination that induces poor mucosal immunity. Another advantages of using mucosal vaccines are high patient compliance, low cost and easy other administration. Despite these advantages, very few mucosal vaccines are commercially available today. This is because mucosal vaccines are prone to degradation in the harsh conditions of the gastrointestinal (GI) tract lowering the bioavailability of antigens to induce immune responses. Therefore, protective and effective formulations are required for successful mucosal vaccination. Accordingly, the use of nano-and micro-polymeric particles has received much attention as delivery vehicles of antigens because they can protect the antigens from degradation in the GI tract and they also enhance the antigen uptake in mucosal-associated lymphoid tissue. Particularly, mucoadhesive polymeric carriers are the most promising vehicles for mucosal vaccine delivery because these carriers retain the vaccines on the mucosal tissues for longer period thus improving the bioavailability of the antigens. Most importantly, M cells on the follicle-associated epithelium of the Peyer's patch play a key role in mucosal infection and immunity because they uptake and deliver antigens across mucosal epithelia to the lymphoid tissues via transcytosis. In this review, we dig the role and characteristics of M cells on mucosal immunization and explore the molecules of M cells for targeted delivery of antigens by polymeric particle system.