This study investigated cellular trafficking and inflammatory markers in orthopedic biomaterial particle-challenged human peripheral blood monocytes (PBMCs) using a murine immunodeficiency (SCID) model. Periprosthetic tissues from aseptic loosening patients were transplanted into muscles of SCID mice. PBMCs from the same patients were stimulated in vitro with Ti-6Al-4V, PMMA, UHMWPE, or Co-Cr particles for 3 days before administered intraperitoneally to the periprosthetic tissue-implanted mice. The xenografts were harvested 2 weeks later for histological and molecular analyses. Significant cell infiltration was obvious in the transplanted tissues from mice transfused with Ti-alloy, PMMA and UHMWPE-provoked PBMCs compared to controls, and UHMWPE-provoked PBMCs group accumulated significantly more cells among all groups. There were ubiquitous TRAP+ stained cells in all xenografts from particle-stimulated PBMCs mice. Immunohistochemical staining indicated that significantly more IL-1 and TNF positive cells occurred in Ti and PMMA groups; while the UHMWPE group resulted in stronger positive MCP-1 and IL-6 stains. Polymerase chain reaction (PCR) confirmed overexpression of both IL-1 and TNF in Ti and PMMA-stimulated groups; and more MIP-1 gene expression developed in the UHMWPE group. Overall, different type of orthopedic materials influenced the trafficking ability of particle-activated PBMCs which may depend on upregulation of various proinflammatory cytokines and chemokines.