Wear debris affects both initial osseointegration and subsequent bone remodeling of total joint replacements (TJRs). To study the complex cascade associated with the continuous generation of particles, a robust animal model is essential. To date, an animal model that incorporates continuously delivered particles to an intramedullary orthopaedic implant has not been available. In this study, we successfully infused clinically relevant ultra high molecular weight polyethylene particles, previously isolated from joint simulator tests, to the intramedullary space of the mouse femur for 4 weeks using a subcutaneous osmotic pump. Reduction of bone volume following the 4-week infusion of UHMWPE was detected by microCT. UHMWPE particles also changed the level of Alkaline Phosphatase expression in the infused femurs. Continuous infusion of particles to the murine bone–implant interface simulated the clinical scenario of local polymer wear particle generation and delivery in humans and can be used to further study the biological processes associated with wear debris particles.