BACKGROUND: Preliminary study has prepared three-dimensional printing β-tricalcium phosphate scaffold loaded with icariin. OBJECTIVE: To investigate the role of three-dimensional printing β-tricalcium phosphate scaffold loaded with icariin in the repair of rabbit models of osteonecrosis of the femoral head. METHODS: New Zealand white rabbits (provided by Qinglongshan Laboratory Animal Center of Nanjing) were selected to establish the steroid-induced osteonecrosis of the femoral head. The 27 model rabbits underwent core decompression and debridement, were randomly divided into three groups, and then implanted with autologous bone, β-tricalcium phosphate scaffold, three-dimensional printing β-tricalcium phosphate scaffold loaded with icariin (composite scaffold group) , respectively. The micro-CT scanning and pathological observation were performed at 4, 8, and 12 weeks after implantation. RESULTS AND CONCLUSION: (1) Micro-CT showed that at 4 weeks after implantation, trabecular bone was observed around and in implants in each group. In the autologous bone group, there were a large number of trabecular bones in the grafting area at 8 weeks, and the trabecular bone structure was dense at 12 weeks after implantation. In the tricalcium phosphate and composite scaffold groups, the scaffolds were well integrated with the bone interface. At 4 weeks after implantation, there was a certain amount of trabecular bone surrounding the scaffold, and trabecular grew into the scaffold until 8 weeks in the composite scaffold group. At 4 weeks after implantation, few thin trabecular bone was visible, and extensive trabecular bone formation was observed around the scaffold at 8 weeks in the tricalcium phosphate group. (2) Hematoxylin-eosin staining results showed that there were many mature osteoblasts, and few cartilage matrix, newly born bones integrated well to the implants at 12 weeks in the autologous bone and tricalcium phosphate groups. In the composite scaffold group, there were many cartilage matrixes, and newly born bones integrated poorly to the implants. (3) Masson staining showed that at 12 weeks after implantation, the osteogenic capacity in the composite scaffold group was lower than that in the autologous bone group (P < 0.05) , but higher than that in the tricalcium phosphate group (P < 0.05) . (4) TRAP staining results at 12 weeks after implantation revealed that the amount of osteoclast in composite scaffold group was less than that in the tricalcium phosphate group (P < 0.05) , and was not significantly different from the autologous bone group (P> 0.05) . (5) Immunohistochemical staining at 12 weeks after implantation revealed that the positive rate of vascular endothelial growth factor in the composite scaffold group was higher than that in the tricalcium phosphate group (P < 0.05) , and lower than that in the autologous bone group (P < 0.05) . (6) In summary, three-dimensional printing β-tricalcium phosphate scaffold loaded with icariin implanted into the rabbit model of osteonecrosis of the femoral head can promote the proliferation and differentiation of osteoblasts, inhibit the viability of osteoclasts, promote the angiogenesis, and contribute to the repair of osteonecrosis of the femoral head in rabbits.