The purpose of this study was to investigate in vivo biocompatibility and osteogenesis as well as degradability of the porous strontium-doped calcium polyphosphate (SCPP) scaffolds as a biomaterial for bone substitute applications. The evaluation was performed on a rabbit model over a period of 16 weeks by histology combined with image analysis, X-ray microradiography and immunohistochemistry methods. The histological and X-ray microradiographic results showed that the SCPP scaffold exhibited good biocompatibility and extensive osteoconductivity with host bone. Moreover, a significant more bone formation was observed in the SCPP group compared with that in the CPP group, especially at the initial stage after implantation. New bone volumes (NBVs) of the SCPP group determined at week 4, 8 and 16 were 14, 27 and 45%, respectively. Accordingly, NBVs of the CPP group were 10, 19 and 40%. Immunohistochemical results revealed that both the expression of collagen type I and bone morphogenetic proteins in the SCPP group were higher than that in the CPP group, which might be associated with the release of strontium ions during the implantation. In addition, during 16 weeks implantation the SCPP scaffold exhibited similar degradability with the CPP scaffold in vivo. Both scaffolds showed the greatest degradation rate for the first 4 weeks, and then the degradation rate gradually decreased. The results presented in this study demonstrated that SCPP scaffold can be considered as a biocompatible material, making it attractive for bone substitute application purposes.