This study was designed to investigate the influence of demineralized bone particles (DBP)/PLGA hybrid scaffold on angiogenesis and osteogenesis in a calvarial defect model. DBP/PLGA scaffolds were manufactured by solvent casting/salt leaching method, and each scaffold contained 0, 10, 20, 40, and 80 wt% DBP of PLGA, respectively. A total of 34 rats were operated and bicortical holes were placed on their calvaria. The defects were filled with different ratio DBP/PLGA scaffolds. After 3, 7, 14, and 28 days, specimens were taken and, histologic, immunohistologic and RT-PCR analyses were carried out concerning number of vessels and density of regenerated bone, and angiogenic activation. On days 7, in all experimental groups, bone formation occurred in a direction from defected margin of calvarium to center of implanted scaffold and new vessel formation took place in front of the osteogenic regeneration front. We found that the 20 and 40 wt% DBP/PLGA scaffold was superior in its ability to regenerate new bone, induced more intensive formation of microvasculature and expressed in a higher level of osteocalcin mRNA than other groups.