Objective: To evaluate the effect of autologous bone marrow mesenchymal stem cells (BMSCs) seeded bio-derived bone materials (BBM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in repairing defect of osteonecrosis of femoral head (ONFH). Methods: Early-stage osteonecrosis in the left hip was induced in 36 adult New Zealand white rabbits (provided by the Animal Center of Guangxi Medical University, Nanning, China) after core decompression and delivery of liquid nitrogen into the femoral head. Then the animals were divided into three groups according to the type of implants for bone repair: 12 rabbits with nothing (GroupⅠ, the blank control group), 12 with BBM combined with rhBMP-2 (Group Ⅱ), and 12 with BMSCs-seeded BBM combined with rhBMP-2 (Group Ⅲ). At 4, 8, and 12 weeks after surgery, X-ray of the femoral head of every 4 rabbits in each group was taken, and then they were killed and the femoral heads were collected at each time point, respectively. Gross observation was made on the femoral heads. After hematoxylin and eosin staining, Lane-sandhu scores of X-ray and bone densitometry were calculated and the histomorphometric measurements were made for the new bone trabeculae. Results: At 12 weeks after surgery, two femoral heads collapsed in GroupⅠ, but none in Group Ⅱor Group Ⅲ. X-ray examination showed that the femoral heads in Group Ⅰ had defect shadow or collapsed while those in Group Ⅱ had a low density and those in Group Ⅲ presented with a normal density. Histologically, the defects of femoral heads were primarily filled with no new bone but fibrous tissues in Group Ⅰ. In contrast, new bone regeneration and fibrous tissues occurred in Group Ⅱ and only new bone regeneration occurrd in Group Ⅲ. Lane-sandhu scores of X-ray, bone mineral density and rate of new bone in trabecular area in Group Ⅲ were higher signifIcantly than those of the other two groups. Conclusions: Our findings indicate a superior choice of repairing the experimental defect of ONFH with BMSCs- seeded BBM combined with rhBMP-2.