OBJECTIVES: To observe the effect of electroacupuncture(EA) on adenosine monophosphate-activated protein kinase (AMPK) signaling pathway and mitochondrial energy metabolism in vascular dementia (VD) rats, so as to investigate its potential mechanisms underlying prevention and treatment of VD. METHODS: Male SD rats were randomly divided into sham surgery group, model group, EA group, non-acupoint group, and EA+inhibitor group, with 8 rats in each group. Except for the sham surgery group, VD model was established in other 4 groups by permanent bilateral common carotid artery ligation. Rats in the EA group received EA at "Baihui"(GV20) and "Shenting"(GV24), while rats in the non-acupoint group received EA at the non-acupoint 10 mm above the iliac crest bilaterally. The EA frequency was 2 Hz/15 Hz, duration was 30 min per session, once a day, for 7 d continuously. Rats in the EA+inhibitor group received intraperitoneal injection of AMPK inhibitor Compound C 2 h before EA intervention. After intervention, Morris water maze test was used to evaluate the learning and memory ability of rats. ELISA was used to detect the contents of mitochondrial complexes I-IV in the hippocampus. Colorimetric method was used to detect the content of adenosine triphosphate (ATP) in the hippocampus. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Western blot was used to detect the protein expressions of hippocampal AMPKα1, fatty acid translocase (FAT)/cluster of differentiation 36 (CD36), and acetyl-CoA carboxylase 2 (ACC2). RESULTS: Compared with the sham surgery group, the escape latency and total distance traveled of rats in the model group increased ( CONCLUSIONS: EA can improve cognitive impairment in VD rats by activating AMPK, up-regulating FAT/CD36 expression, and down-regulating ACC2 expression, thereby promoting mitochondrial fatty acid metabolism and improving mitochondrial morphology and function.