Objective To determine the expression of the Dlx 2 gene in skull tissue of the small?tailed Han sheep skull defect model, and to investigate its significance in this skull defect. Methods Ten small?tailed Han sheep aged one month old were selected to establish the skull defect model. Newborn skull tissue in the defect area and native skull tissue adjacent to the defect area were collected. Dlx 2 expression at the mRNA and protein levels was determined by real?time PCR and western blotting. Results Compared with the levels in native skull tissue adjacent to the defect area, the Dlx 2 mRNA and protein expression of newborn skull tissue in the defect area was significantly increased ( P < 0. 05). Conclusions Increased Dlx 2 gene expression may play an important role in the repair of skull defects.