A few studies have reported a relationship between leptin induced by brain injury and healing of bone tissue. Our objective was to measure serum and callus leptin expression within the setting of fracture and traumatic brain injury (TBI). Sixty-four male Sprague-Dawley rats were randomised equally into four groups: control, TBI group, fracture group and fracture/TBI group. Rats were sacrificed at 2, 4, 8 and 12 weeks after fracture/TBI. Serum leptin was detected using radioimmunoassay, and callus formation was measured radiologically. Callus leptin was analysed with immunohistochemistry. Serum leptin was significantly increased in the fracture, TBI and combined fracture/TBI groups compared with the control group at 2 weeks (P < 0.05). Serum leptin was significantly higher in the combined fracture/TBI group than in the fracture and TBI groups at 4 and 8 weeks (P < 0.05). The percentage of leptin-positive cells in the callus and callus volume were significantly higher in the fracture/TBI group than in the fracture-only group (P < 0.001). Thus, we demonstrated elevated leptin expression within healing bone, particularly in the first 8 weeks of a rat model combining fracture and TBI. A close association exists between leptin levels and the degree of callus formation in fractures.