Objective To explore the mechanism by which acupuncture wakes rats from traumatic brain injury (TBI) coma. Methods SD rats were divided randomly into blank, model, solvent control, acupuncture, and purinergic P2RX7 antagonist(anti-P2RX7)groups ( n= 12 rats per group). The model was established by controlled cortical impact. Rats in the solvent control, acupuncture, and anti-P2RX7 groups were injected with DMSO solution or P2RX7 antagonist in the periaqueductal gray ( vPAG) area of the midbrain for 30 min, respectively. After establishing the model, rats in the acupuncture and anti-P2RX7 groups were given acupuncture at Baihui and Shuigou points. Behavior was evaluated by coma time, state of consciousness, and modified neurological severity score (mNSS). The morphology of the vPAG area was observed by hematoxylin-eosin(HE) and Nissl staining, dopamine (DA) levels were detected by ELISA, and P2RX7 and dopamine transporter (DAT) expression were detected by immunofluorescence, Western Blot, and RT-qPCR. Results Compared with those in the blank group, rats in the model, solvent control, and anti-P2RX7 groups had prolonged coma durations, and increased consciousness and mNSS at each time point ( P<0. 05), increased pathological changes including neuronal degeneration, nuclear condensation, and Nissl’s corpuscle in the vPAG, and reduced DA, P2RX7, and DAT expressions in the vPAG (P<0. 05). Consciousness scores at 2. 5 and 4 hours after TBI, and mNSS at 12 hours after TBI were increased in the acupuncture group (P<0. 05), and pathological changes including neuron degeneration, nuclear condensation, and increased Nissl’s corpuscles existed in the vPAG. Compared with the findings in the model group, in the acupuncture group, the coma duration was shorter, the consciousness state and mNSS at each time point were decreased ( P<0. 05), tissue and neuron damage in the vPAG were reduced, and the DA level and P2RX7 and DAT expression were increased (P<0. 05). Compared with the findings in the solvent control group, in the acupuncture group, the coma duration was shortened, consciousness scores at 12, 24, and 48 h after TBI and the mNSS at 24 and 48 hours after TBI were decreased (P<0. 05), tissue and neuron injury in the vPAG were reduced, and DA, P2RX7, and DAT expression were increased (P<0. 05). Compared with the findings in the acupuncture group, in the anti-P2RX7 group, the coma duration was prolonged, the consciousness score and mNSS at each time point were increased (P<0. 05), tissue and neuron damage in the vPAG were increased, and DA, P2RX7, and DAT expression were decreased ( P<0. 05). Conclusions Acupuncture at GV20 and GV26 may regulate DA metabolism by upregulating P2RX7 expression, restoring pathological changes in the vPAG, improving the consciousness state and neurological function, and promoting coma awakening in rats after TBI.