Purpose: The influence of bone marrow in the osteogenic potential of bone has not been evaluated in the rabbit tibia model. Previous studies employed this model extensively to test the osteogenic capabilities of bone grafts. The primary aim of the present study was to assess the role of bone marrow in the healing of experimental defects in the rabbit tibia model. Materials and Methods: Ten New Zealand rabbits were divided into two groups of five each. In the first experimental test group (PoP), the marrow cavity was emptied completely under a 6-mm defect in the rabbit tibia metaphysis; the marrow was replaced by plaster of Paris, and a round piece of lyophilized collagen membrane was placed in contact with the endosteum and rested on the plaster. In the second experimental group (control), similar artificial defects were made, but the marrow was left intact. After 8 weeks, the animals were sacrificed and prepared for histologic and histomorphometric analysis. Results: There was a statistically significant difference (P = .016) in newly formed bone area between the control group (mean, 68.08% ± 12.09%) and the PoP group (mean, 54.02% ± 13.93%). Similarly, there was a statistically significant difference in new bone density (P .001) between the control group (mean, 95.99% ± 1.74%) and the PoP group (mean, 75.37% ± 13.27%). Conclusions: The current study confirms the significant effect that bone marrow has in bone regeneration and also the true regenerative capabilities of the osseous walls of the defects. The proposed experimental model may be a more reliable method of investigating and comparing the potential of different graft materials and methods. Keywords: bone marrow, bone regeneration, plaster of Paris, rabbit tibia