Peyer’s patches have a potential role not only in the mucosal but also in the systemic immune responses against pathogens. Recently, Peyer’s patches and their immune cells are important to be targeted with proteins or antigens for nanobiology and nanomedicine applications. Nanoparticles have several advantages as good models for vaccine delivery. Nanoparticles uptake by Peyer’s patches introduces the possibility of accommodate vaccines for oral immunization. Particle size is one of the most important factors in the uptake and pathway of nanoparticles into the gastrointestinal tract especially Peyer’s patches. In this work, thiol-organosilica particles have characteristics such as controllable size, surface charge (approximately -50 mV), mucoadhesive and possess surface mercaptopropyl residues containing alkyl chains and thiol residues. These factors might be optimal for studying vaccine delivery and the immunological interactions between particles size and immune cells such as M cells of Peyer’s patches and plasma cells of villi lamina propria. This work introduces important information of the peyer’s patches immune responses using different sizes of organosilica particles.