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Purpose: We administered recombinant interleukin 01)-4 and recombinant IL-13 locally into the air pouch of mice to improve bone resorption induced by ultra-high-molecular-weight polyethylene (UHMWPE) particles.Methods: Air pouches were established on the back of BALB/c mice, followed by the surgical introduction of a section of calvaria from a syngeneic mouse donor.We stimulated the bone-implantod pouches with the UHMWPE suspension.We divided UHMWPE-containing mice into four study groups to receive injections of phosphate-buffered saline (control),IL-4 alone, IL-13 alone, or IL-4 and IL-13 into the pouches.We harvested the tissues at 14 d after treatment for molecular and histological analyses.Results: The inhibitory effect of IL-4 was stronger than that of IL-12 toward osteoclast differentiation and osteoblast for the induction of osteoprotegerin production and down regulation of receptor for activation of nuclear factor-κB ligand production.Furthermore,the combined treatment with both IL-4 and 1L-13 had a more important role in inhioiting bone resorption in these pouches with UHMWPE stimulation, compared with IL-4 or IL-13 treatment alone.Conclusions: Local administration of recombinant IL-4 and IL-13 may be a feasible and effective therapeutic candidate to treat or prevent wear debris-associated osteolysis.