Particles released from biomaterials may migrate into various tissues and lead to the activation of the host s inflammatory and immune responses. This study evaluated the relevance of size and chemical composition on particle distribution in the mouse tissues following intraperitoneal injection with polymethyl methacrylate (PMMA) particles (1.4 and 6.4 um) and polystyrene (PS) particles (1.2, 5.2, and 12.5 um). Macroscopic examination of the tissues at 1,7, and 24 days revealed accumulations of the colored PS particles in the adipose tissue adjacent to the spleen, pancreas, and caudal to the stomach. Histologic examination of the tissues revealed PS particles in the adipose tissues adjacent and in the splenic capsule. In contrast, PMMA accumulated in the splenic tissue. The spleens were enlarged and very cellular. These results indicate that PS and PMMA particles induce different patterns of particle distribution and intensities of the host response.