Objective To explore the mechanism of acupuncture in waking coma rats after traumatic brain injury (TBI). Methods SD rats were randomly divided into blank group, model group, solvent control group, acupuncture group and purinergic P2RX7 receptor antagonist group, with 12 rats in each group. The model was established by controlled cortical impact (eCCI). The solvent control group, acupuncture group and P2RX7 antagonist group were injected with DMSO solution or P2RX7 antagonist in the periaqueductal gray (vPAG) area of midbrain for 30min, respectively. After the model was established, the acupuncture group and P2RX7 antagonist group were given acupuncture at Baihui and Shuigou points. Behavior was evaluated by coma time, state of consciousness and mNSS score. The morphology of vPAG area was observed by HE and Nissl staining, the level of dopamine (DA) was detected by ELISA, and the expression of P2RX7 and dopamine transporter (DAT) was detected by immunofluorescence, Western Blot and RT-qCPR. Results Compared with the blank group, in the model group, solvent control group and P2RX7 antagonist group, the duration of coma was prolonged, the state of consciousness and mNSS score at each time point were increased (P < 0.05), and pathological changes such as neuronal degeneration, nuclear condensation and Nissl's corpuscle increased in vPAG area, and the DA level, P2RX7 and DAT expressions in vPAG area were decreased (P < 0.05). In acupuncture group, the coma duration, the scores of conscious state at 2.5 hours and 4 hours after TBI and the mNSS score at 12 hours after TBI were increased (P < 0.05), and some pathological changes such as degeneration of neurons, nuclear condensation and increase of Nissl's corpuscles existed in vPAG area. Compared with the model group, the duration of coma in acupuncture group was shortened, the conscious state and mNSS score at each time point were decreased (P < 0.05), the damage of tissues and neurons in vPAG area was reduced, and the DA level, P2RX7 and DAT expression were increased (P < 0.05). Compared with the solvent control group, the duration of coma in acupuncture group was shortened, the scores of consciousness at 12 hours, 24 hours and 48 hours after TBI and the scores of mNSS at 24 hours and 48 hours after TBI were decreased (P < 0.05), the injury of tissues and neurons in vPAG area was reduced, and the expression of DA, P2RX7 and DAT were increased (P < 0.05). Compared with acupuncture group, the duration of coma in P2RX7 antagonist group was prolonged, the scores of consciousness and mNSS at each time point were increased (P < 0.05), the damage of tissues and neurons in vPAG area was increased, and the expression of DA, P2RX7 and DAT was decreased (P < 0.05). Conclusion Acupuncture at GV20 and GV26 may regulate the metabolism of DA system by up-regulating the expression of P2RX7, restore the pathological changes in vPAG area, improve the state of consciousness and neurological function, and then promote the awakening of coma rats after TBI.