Objective To observe the early neuroprotective effect of shenzhiling oral liquid on AD mice, andto observe the effect of shenzhiling oral liquid on the ultrastructure of myelin sheath and synapse in CA1 area ofhippocampus and the changes of special staining of myelin sheath. Methods The App / Ps1 transgenic mouse model isformed by PrP-hAppk595N / M596L single transgenic dementia model mice and PrP-hPs1dE9 single transgenicdementia model mice, which is a common disease model to study Alzheimer’ s disease. The 3-month-old App / Ps1double-transgenic mice were randomly divided into the following groups (n = 9 per group): model group, donepezilgroup [0. 92 mg/ (kg·d)], shenzheling high-dose group [50 g/ (kg·d)], shenzheling medium-dose group [25 g /(kg·d)], and shenzheling low-dose group [12. 5 g/ (kg·d)]. C57BL/6J mice of the same age and background wereused as the control group. After 3 months of continuous intragastric administration, the hippocampal CA1 tissue ofmice was obtained for electron microscopic analysis, and the ultrastructural changes of myelin sheath and synapses inthis area were observed. The myelin sheath was stained and analyzed by luxol fast blue staining of nerve myelins.Results The number of synapses in the hippocampal CA1 area was decreased in the model group compared withcontrols ( P < 0. 01); the structure of neurons showed degenerative changes, the morphology of oligodendrocytesshowed pre-apoptotic state, and the structure of myelin sheath layer collapsed. The number of synapses in thehippocampal CA1 area of mice in each drug intervention group was increased compared with the model group ( P <0. 01); the morphological structure of neurons and oligodendrocytes was relatively complete, the morphologicalstructure of neurons and oligodendrocytes was intact, the chromatin was uniform, and the myelin lamellar structure wasimproved. Luxol fast blue staining revealed that myelin fibers in the model group were significantly decreased and thestaining was lighter than that in the control group. The myelin fibers in the intervention groups were increased andstaining was deepened to different degrees. Conclusions Shenzheling oral liquid may play an early neuroprotectiverole in Alzheimer’s disease by increasing the number of synapses in the hippocampal CA1 area of App / Ps1 transgenic mice and improving the structure and morphology of myelin sheath, oligodendrocytes and neurons.