Osteolysis after single-injection polyethylene (PE) administration has been analyzed, but this experimental model did not reflect the clinical postoperative condition. Therefore, we investigated the bone-resorbing cytokines interleukin and tumor necrosis factor (IL-1alpha, IL-6, TNFalpha) produced by continuous PE administration using histomorphologic findings and the reverse transcription polymerase chain reaction. TNFalpha mRNA was continuously detected in the PE continuous-infusion group, whereas it was not expressed in the PE single-injection group. IL-1alpha and IL-6 mRNA were detected in both groups. As for histomorphological findings, in the PE continuous-infusion group proliferating fibrous tissue penetrated subchondral bone and the interface membrane around the K-wire inserted into the femur. Numerous osteoclasts were observed in the vicinity of resorbed bone. In the PE single-injection group, proliferation of fibrous tissue with bone resorption was not observed. TNFalpha may play a major role in fibrous tissue formation and osteoclastic bone resorption caused by PE debris. This osteolysis model is useful for investigating osteolysis associated with bone-resorbing cytokines under conditions similar to those seen with a human prosthesis.