Objective: Shenmayizhi decoction (SMYZ) a Chinese herbal formula which is prescribed by an experienced traditional Chinese medicine (TCM) clinician and has proven efficacy in animal experiments and clinical trials in the treatment of vascular dementia (VaD). In this study, we attempted to predict the underlying mechanisms of SMYZ in treating VaD. Methods: Using online databases, the active compounds in SMYZ were screened and corresponding biological targets predicted. After establishing herb-target and compound-target networks, we analyzed the synergistic effect of the four herbs in SMYZ. VaD-related genes were mined from online databases such as OMIM and Malacards and their pathways were enriched to determine the principal pathways contributing to VaD pathology. SMYZ targets and VaD-related genes were intersected subsequently to get the common targets, which were defined as directly intervening targets (DITs) of SMYZ in treatment of VaD. Then herb-DIT and compound-DIT networks were constructed to explore the direct regulatory pattern of the herbs and compounds in SMYZ when treating VaD. Protein-protein-interaction (PPI) networks of DITs were constructed and all the genes (n=50) in the PPI network were analyzed by pathway enrichment. Results: It was found that SMYZ may treat VaD by regulating the prteins in the cerebral endothelium involved in the pathway of 'fluid shear stress and atherosclerosis'. Conclusion: Network pharmacology could be a good method in the prediction of mechanism of Chinese herbal formula in treating different diseases.