OBJECTIVE: To explore the neuroprotective mechanisms of Tongluo Huatan capsule(THC) in a rat model of vascular dementia(VD).METHODS: A rat model of VD was established by repeated clamping of bilateral common carotid arteries with the intraperitoneal injection of sodium nitroprusside solution. VD rats were administered THC, memantine hydrochloride, or distilled water daily for 14 d after operation. Learning and memory abilities were assessed using the step-down passive avoidance test, novel object recognition(NOR)test, and Morris water maze(MWM) test. Pathological changes in the hippocampus were observed through hematoxylin and eosin and Nissl staining.The expression levels of clathrin, RAB5 B, andN-methyl-D-aspartic acid receptor 1(NMDAR1)were measured by immunohistochemistry staining,real-time quantitative polymerase chain reaction and Western blot.RESULTS: Rats in VD group showed impaired learning and memory abilities(step-down passive avoidance, NOR, and MWM) and abnormalities in neuronal morphology(light microscopy) in the hippocampus. The m RNA or protein expression levels of clathrin and RAB5 B were decreased, and NMDAR1 was increased in hippocampal tissues(P < 0.05). Administration of THC promoted the learning and memory abilities and the morphological structure of hippocampal neurons in VD rats. Besides, THC enhanced m RNA or protein expression levels of clathrin and RAB5 B, and decreased NMDAR1(P < 0.05).CONCLUSION: THC may improve cognitive functions by regulating the endocytosis of NMDA receptors mediated by clathrin.