Aseptic loosening of artificial joints is the most common complication after artificial joint replacement. Finding the solution to tackle aseptic loosening of artificial joints is a focus in bone and joint surgery research field. In vitro studies of Sr-doped calcium polyphosphate (SCPP) have found by our team that it could promote osteoblast proliferation and inhibit osteoclast activity, and it has a potential inhibitory effect on aseptic loosening by suppressing the expression of receptor activator of nuclear factor-κ B ligand and improving the expression of OPG. The present study aims to confirm the conclusion in vitro by the mean of animal experiment. The Ti rod prosthesis coated with SCPP, calcium polyphosphate (CPP), and Ultra-high molecular weight polyethylene (UHMWPE were implanted in the femur (the internal surface of bone tunnel was also coated with SCPP, CPP and UHMWPE respectively). Radiography (x-rays, micro-CT), histochemistry (Hematoxylin-eosin staining (HE), methylene blue-acid fuchsin, Von Kossa histological staining), molecular biology (alkaline phosphatase and TRAP5b factors, Mir21-5p and Mir 26a-5p) were performed to analyzed the effects of SCPP within 20 weeks. The Radiography results showed that osteolysis with various severity occurred in all groups, and SCPP group had the mildest osteolysis. Histochemistry results showed that arthritis was milder in SCPP and CPP groups, while the bone formation in SCPP group was most significant. Its bone reconstruction effect was the best as well. The Molecular biology results showed that the bone reconstruction was out-sync in each group. Compared with other groups, the bone resorption occurred at the latest and the bone resorption time was the shortest in experimental animals of SCPP group. All results indicated that SCPP could promote osteoblast activity and bone reconstruction, improve the integration of bone interface between prosthesis and base bone, reduce osteoclast activity and shorten the osteoclast action time at the implantation site in vivo. Thus, it could postpone or alleviate the occurrence and development of aseptic loosening in vivo. Therefore, SCPP could be a promising material for the construction of artificial joints with the ability to resist aseptic loosening.