The design and synthesis of materials capable of activating the immune system in a safe manner is of great interest in immunology and related fields. Lactobacilli activate the innate immune system of a host when acting as probiotics. Here, we constructed lactobacilli-mimicking materials in which polysaccharide peptidoglycan complexes (PS PGs) derived from lactobacilli were covalently conjugated to the surfaces of polymeric microparticles with a wide variety of sizes, ranging from 200 nm to 3 mu m. The artificial lactobacilli successfully stimulated macrophages without cytotoxicity. Importantly, we found that the size of artificial lactobacilli strongly influenced their immunostimulating activities, and that artificial lactobacilli of 1 mu m exhibited 10-fold higher activity than natural lactobacilli. One major advantage of the artificial lactobacilli is facile control of size, which cannot be changed in natural lactobacilli. These findings provide new insights into the design of materials for immunology as well as the molecular biology of lactobacillus.