Objective To investigate the change in the expression level of silent information regulator related enzyme 1 （SIRT1） based on the p38 mitogen-activated protein kinase （p38MAPK） signaling pathway in rats with severe traumatic brain injury and its effect on post-traumatic stress disorder （PTSD）.Methods A total of 80 Sprague-Dawley rats were selected， among which 15 rats were established as control group and the rest of the rats were used to establish a rat model of severe traumatic brain injury and were then divided into model group， SIRT1 overexpression group， and p38 agonist group. The rats in the control group were given sham operation model， those in the SIRT1 overexpression group were given intracerebral injection of SIRT1 overexpression lentiviral vector， and those in the p38 agonist group were given SIRT1 overexpression lentiviral vector+p38 agonist； the rats in the model group and the control group were given an equal volume of normal saline. Neurological function was evaluated on days 1， 3， and 5 after trauma； the elevated plus maze test was used to evaluate post-traumatic stress behavior； the TTC method was used to observe the area of cerebral infarction； Western blotting was used to measure the protein expression of SIRT1， p38， and p-p38 in the cerebral cortex at the ipsilateral side.Results Neurological score gradually decreased from the model group to the p38 agonist group， the SIRT1 overexpression group， and the control group （P <0.05）， with gradual increases in the number of times of entering open arm （and closed arm） and the time spent in open arm （and closed arm） （P <0.05）. The model group， the SIRT1 overexpression group， and the p38 agonist group had marked cerebral infarction on days 1， 3， and 5 after trauma， which aggravated over time， and the SIRT1 overexpression group and the p38 agonist group had certain improvement compared with the model group. The relative protein expression of SIRT1 and p-p38 gradually increased from the model group to the p38 agonist group， the SIRT1 overexpression group， and the control group （P <0.05）.Conclusion The expression of SIRT1 is downregulated in the cerebral cortex of rats with severe traumatic brain injury， and upregulation of SIRT1 can alleviate PTSD， possibly by inhibiting the p38 signaling pathway.