Introduction: So far, various methods have been used to accelerate the bone healing process. Among these methods is platelet-rich plasma (PRP) or platelet concentrate (PC), which provides high concentrations of growth factors. The aim of the present study was to compare the effect of Leucocyte and platelet-rich fibrin (L-PRF) and advance platelet-rich fibrin plus (APRF+) with biphasic calcium phosphate HA/βTCP (BCP) on bone regeneration by histological and histomorphometric investigation in Calvaria of rabbits. Materials and Methods: In the parietal bone of 12 rabbits, 4 bony defects were created and divided into 4 groups. 1) Control that was left blank, 2) HA/βTCP, 3) HA/βTCP + L-PRF, and 4) HA/βTCP + APRF Plus. Rabbits were randomly divided into 2 groups so that 6 rabbits were sacrificed at week 4 and the rest at week 8. The prepared samples were examined microscopically and histomorphometrically. Findings: In the group filled with BCP along with LPRF in the first and second months, the amount of newly formed bone was significantly higher than the BCP group alone. In concurrent use with APRF+, the amount of new bone formation was greater compared to other groups in the first month, and the cavity was filled with mature bone in the second month. Overall osteoblast, osteocyte, and osteon amounts were specifically higher in BCP+LPRF and BCP+APRF plus groups than other groups. In addition, all three treatment groups showed a significantly higher amount of osteon than the control group in the second month. Conclusion: BCP alloplast substance in combination with LPRF or APRF+ shows a higher amount of ossification compared to the use of bone substitute substance alone.