Objective To investigate the biomechanical changes in the osteonecrosis of the femoral head (ONFH) of rabbits treated by neuropeptide gene (calcitonin gene-related peptide α, hCGRPα)-transfected stem cells combined with autologous bone grafting. Methods The ONFH models on one side in rabbits were established by liquid nitrogen. Forty-eight rabbits ONFH models were randomly divided into 3 groups: group A [hCGRPα-transfected bone marrow mesenchymal stem cell (BMSCs) group], the hCGRPα was transfected into BMSCs combined with autologous bone graft into the femoral head; group B (BMSCs group), BMSCs were transfected with empty plasmid (only pLNCX2 plasmid) combined with autologous bone graft; group C (irrelated sequence group), BMSCs were transfected with irrelated gene combined with autologous bone graft. Animals were sacrificed at 3rd and 6th month respectively to observe the biomechanical changes in the femoral head of rabbits. Results At 3rd month after surgical treatment, in groups A, B, and C the maximum compressive strength and mean elastic modulus of the subchondral bone of femoral head on surgically treated side respectively were (29.13±1.95) and (59.61±2.18), (24.63±1.35) and (48.87±2.15), (25.05±1.34) and (50.13±2.28) mPa, and those of the cancellous bone of femoral head on surgically treated side respectively were (16.41±1.13) and (24.11±2.32), (11.43±1.55) and (17.63±2.45), (12.51±1.85) and (18.22±2.32) mPa. The biomechanical strength was the best in the femoral head in group A, which was nearly close to that in the normal side (P>0.05) and was significantly greater than that in both group B and group C (P 0.05). Conclusion hCGRPα-transfected BMSCs combined with autologous bone grafting into the femoral head of ONFH animal model can accelerate osteogenesis, enhance bone tissue repair, and then effectively recover the normal biomechanical properties of the femoral head. Key words: Calcitonin gene-related peptide; Bone marrow mesenchymal stem cells; Bone grafting; Osteonecrosis of the femoral head; Biomechanics; Rabbit