OBJECTIVE: To observe the effect of scalp acupuncture on the expression of argarginine vasopressin receptor-1a(VR), phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ), and aquaporin 4(AQP) at hypothalamus in middle cerebral artery occlusion (MCAO) rats, so as to explore the molecular mechanisms of scalp acupuncture reducing encepha-ledema in acute ischemic stroke. METHODS: A total of 96 male SD rats were randomly divided into normal， model, inhibitor and scalp acupuncture groups, with 24 rats in each group. The MCAO model was established by thread occlusion method. The inhibitor group was intraperitoneally injected with VR inhibitor (30 μg/kg)，once a day for 7 consecutive days. In the scalp acupuncture group, acupuncture was applied to bilateral "parietal and temporal anterior oblique line", with rapid insertion of 2 needles at 15° to 20°, twisting at 100 r/min for 1 min, and retaining the needles for 30 min, once a day for 7 consecutive days. The neurologic deficit score (NDS) and neurological score (NS) were evaluated before and after intervention. The positive expression of p-CaMKⅡ and AQP proteins in hypothalamus was detected by immunohistochemistry. The water content of left brain tissue was determined by BIIiot method. The expression of VR mRNA in hypothalamus was detected by real-time PCR. RESULTS: Compared with the normal group, the NDS, NS, hypothalamic VR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP positive expression levels were significantly increased (<0.01) in the model group. Compared with the model group, the NDS, NS, hypothalamic VR mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP positive expression levels were significantly decreased (<0.01) in the inhibitor and scalp acupuncture groups. CONCLUSION: Regulating the signaling pathway of VR/CaMKⅡ/AQP in hypothalamus may be one of the molecular mechanisms of scalp acupuncture reducing encephaledema in acute ischemic stroke.