OBJECTIVE: To investigate the efficacy of icariin for healing skull defects in rabbit models.METHODS: Thirty-six 3-month-old female New Zealand white rabbits, weighing 1.8-2.0 kg each, were randomly divided into either the control or experimental group. Skull defect models were constructed in both groups, with the experimental group receiving oral icariin afterwards. At 4, 8 and 12 postoperative weeks, the rabbits were euthanized, and X-rays and samples were taken. Tissue sections were stained using hematoxylin and eosin, followed by additional processing using histological and bone metrological methods for observing the rate and quality of the bone formation.RESULTS: Histologically, additional mature lamellar bone formed in the defect area in the experimental group compared with that of the control group.Bone metrological methods showed that the bone mass, trabecular bone width and number of osteoblasts in the experimental group were significantly higher than those of the control group(P < 0.01).The number of osteoclasts did not significantly differ between the two groups(P > 0.05).CONCLUSION: Icariin increased the bone mass and improved the condition of the defect area in the rabbit skulls.