Objective To establish and evaluate a standardized animal model of femoral fracture combined with sciatic nerve injury in mice. Methods A total of 96 male C57BL/6J mice were randomly divided into 2 groups: femoral fracture combined with sciatic nerve injury group (n＝48) and femoral fracture group (n＝48). The left sciatic nerves were crushed by hemostatic forceps, and the ipsilateral femurs were cut and fixed with intramedullary nails in the bone marrow. And then, the mouse model of femoral fracture combined with sciatic nerve injury was established in femoral fracture combined with sciatic nerve injury group. Mice in the femoral fracture group underwent fracture of the left femurs by intramedullary nails fixation, and the left sciatic nerves were dissociated, but not clamped. Behavioral observation of postoperative mice was performed in both groups. The left sciatic nerves of mice were collected in both groups (36 mice each) on the 3^rd, 5^th, 7^th, 10^th, 14^th and 18^th d after operation, with 6 mice in each group at each time point, and the histological changes of the sciatic nerves were observed by immunohistochemical staining. On the 7^th, 14^th, 21^st and 28^th d after operation, the fracture healing was analyzed by femoral X-ray radiographs, micro-CT, hematoxylin-eosin staining and safranine-fast green staining. Results A mouse model of femoral fracture combined with sciatic nerve injury was successfully established. Behavioral observation and assessment revealed that the gait of mice in the femoral fracture combined with sciatic nerve injury group basically returned to normal on the 14^th d after operation. The immunohistochemical results of sciatic nerves showed that the structural continuity of sciatic nerve fibers was basically recovered in the mice of femoral fracture combined with sciatic nerve injury group on the 14^th d after operation. Micro-CT showed that the bone volumes of femoral fracture combined with sciatic nerve injury group were significantly lower than those of femoral fracture group at all time points (all P＜0.01), and so were the bone volume/tissue volume (all P＜0.01). The histomorphological results of bone sections showed that on the 7^th d calluses almost disappeared at the fracture site; however, a small amount of cartilage calluses appeared on the 14^th d, which were mainly composed of undifferentiated mesenchymal stem cells; the cartilage calluses began to calcify on the ²¹st d, and there were some hypertrophic chondrocytes in the calluses; and on the ²⁸th d, new bone formed, containing a large number of hypertrophic chondrocytes, osteoblasts and osteocytes. Conclusion A mouse model of femoral fracture combined with sciatic nerve injury is successfully constructed, and it has a good healing process and delayed healing compared with that of simple femoral fracture, and can better simulate the bone repair and healing process after clinical fracture combined with peripheral nerve injury.