Purpose: The aim of this study was to evaluate the effect of 4-hexylresorcinol and hydroxyapatite combination graft on bone regeneration in the rabbit calvarial defect model. Methods: Ten New Zealand white rabbits were used for this study. Bilateral round shaped defects (diameter: 8.0 mm) were created on the parietal bone. 4-hexylresorcinol and hydroxyapatite combination graft material was grafted into the right parietal bone defect area (experimental). The left bone defect area was not filled with anything (control). The animals were sacrificed at 4 weeks and 8 weeks after grafting. A micro-computerized tomography of each specimen was taken, and the specimens were stained for histological analysis. Results: The average value of bone mineral density (BMD) and Bone volume (BV) was higher in the experimental group than in the control group at 4 weeks and 8 weeks after surgery. However, the difference was not statistically significant (P>0.05) at 8 weeks after grafting. The BMD and BV in the experimental group at 4 weeks after surgery was significantly higher than those in the control group (P ＜0.05). Conclusion: 4-hexylresorcinol and hydroxyapatite combination graft material showed higher initial bone formation than the control, however, there was no difference at 8weeks after operation.