Background: Recently, many reports at home and abroad have indicated that subhypothermia may improve prognosis of nerve function after cerebral ischemia and cerebral injury. But the protection mechanism to brain is not definite. Especially, no research has been done in molecular biological level. Objective: To explore subhypothermia therapy to traumatic brain injury and the possible mechanism in molecular biological level. Design: A randomized and controlled study. Unit: Department of Anesthesiology, Department of Laboratory Medicine, and Department of Neurosurgery in Beijing Tiantan Hospital. Setting and materials: The experiment was done in Beijing Neurosurgery Institute affiliated to Capital University of Medical Sciences. Forty-two healthy Wistar rats were randomly divided into 3 groups: Fifteen in normal temperature group, 15 in subhypothermia and 12 in sham-operation group. Interventions: The model of traumatic brain injury hit from one side was made by hydraulic equipment in normal temperature group and subhypothermia group. Brain temperature was maintained at 37 °C to 38 °C and 33 °C to 34 °C in the early stage (5 minutes) after trauma respectively. The rats in sham-operation group were given the same dealing with normal temperature group except no trauma. After 1 hour temperature control, the brains of five rats in each group were perfused and excised. The expression product of c-Fos, Fos protein was shown by frozen section immunohistochemical staining. The rest rats were put back to the animal house. Death rate in 24 hours was observed and motor function score was given. Main outcome measures: 1 motor function score; 2 the expression product of c-Fos, Fos protein expression; 3 Death rate in 24 hours. Results: Death rate in 24 hours related to injury in subhypothermia group (10%) was significantly lower than that in normal temperature group (10%) (χ2 = 5.495, P < 0.05). Muscle force of the front limbs and thrust from one side and climb power in subhypothermia was scored [(3.0 ± 0.7), (2.7 ± 0.7), (3.0 ± 0.7)] which was improved much more than that in normal temperature group [(1.8 ± 1.0), (1.5 ± 0.6), (1.8 ± 0.5)] (t = -2.655, - 2.88, 3.165, P < 0.05). Fos expression of injury side cortex in subhypothermia (3.0 ± 0.7) increased more than that in normal temperature group (1.2 ± 0.4) (t = -4.811, P < 0.01). Conclusion: Subhypothermia has therapeutic function to TBI. The mechanism may have some relationship with increase of Fos expression.