The present study was designed to investigate whether mechanical testing in conjunction with microcomputed tomography (μCT) analysis can be used to evaluate the quality of regenerated bone enhanced by the implantation of a composite composed of granular octacalcium phosphate and collagen (OCP/Col) matrix. Previous studies confirmed that the granules of OCP alone or OCP in Col matrix tend to mature into bone-like hydroxyapatite and enhance bone regeneration coupled with its own biodegradation, if implanted in various bony sites. OCP/Col was implanted in rat calvaria critical-sized bone defect for 4 to 12 weeks for microindentation, mechanical testing, μCT imaging, and histological examinations. The microindentation testing of the regenerated bone revealed a progressive increase of the Vickers hardness showing the highest value in 12 weeks. The Vickers hardness was in good agreement with both the parameters of μCT and the mechanical property; the quality of regenerated bone increased progressively with the implantation periods. The regenerated bone exhibited a mature bone-like matrix structure with osteocytes histologically. The quality of the regenerated bone was compatible to that of normal control calvaria bone regarding the mechanical properties. The results indicate that microindentation testing can be used to evaluate the quality of regenerated bone in the initial regeneration and the development of bone enhanced by OCP granules within Col matrix. It appears that the implantation of OCP/Col could be a model study to determine the quality of the regenerated bone.