Background: Although quite a number of researches have related to the interventions of Chinese traditional medicine to animal pattern of experimental Alzheimer disease (AD), it is still a blank field for pharmacodynamics research on ideal AD animal model with behavioral changes, typical neuropathological characteristics as well as neurobiochemical changes. Objective: To observe the effects of compound zhinao capsule on learning, memory, cholinergic neurotransmitter in cerebral cortex, hippocampus of experimental AD model rats in order to provide effective treatment medicine for AD. Design: Randomized case controlled study. Setting and participants: This study was completed in School of Life Science of University of Science and Technological of China, Neurological Laboratory of Xuanwu Hospital of Capital University of Medical Sciences and First Affiliated Hospital of Anhui College of Traditional Chinese Medicine (Level 3 Laboratory of National Traditional Medicine). All rats are male with weight between 250 g to 300 g which are purchased from Experimental Animal Centre of Anhui Medical Research Institute. They were randomly divided into normal group, model group, control group (model + naofukang), zhinao I group (model + zhinao capsule I group) and zhinao II group. Interventions: β-amyloid was injected into lateral ventricle of rats combining with TGF-β 1 by research staff according to the overseas literature in order to establish an experimental AD model with both behavioral changes (learning and memory disturbance) and typical pathological (deposit patch of β-amyloid protein) and neurobiochemical characteristics. Compound zhinao capsule was administrated to the model rats to conduct pharmacodynamic research of its effects on learning, memory as well as the cholinergic neurotransmitters in cerebral cortex and hippocampus areas. zhinao capsule was given by stomach perfusion with dose of 2.0 g/(kg per day) and 4.0 g/(kg per day) respectively to rats while rats in normal group and model groups were given same volume saline for stomach perfusion. Rats in control group were administered naofukang suspension with the dose of 100 mg/(kg per week) for 28 days. Water maze method and step-down method were used to test the learning and memory abilities(mean latent period) and passive avoidance reaction (stay rate in bright room) of AD model rats while radio immunity method was applied to detect the contents of acetylcholine (Ach) in cerebral cortex and hippocampus, as well as the activities of choline acetyltransferase (ChAT), acetylcholinesterase (AchE). Main outcome measures: Effects of zhinao capsule on learning, memory and passive avoidance reaction to AD model rats. Effects of zhinao capsule on the activities of ChAT, AchE in cerebral cortex, hippocampus and the content of Ach. Results: In rats of experimental AD model, the mean latent period of water maze greatly increased with the advance of time, the staying rate in bright room greatly decreased(28.7%), the content of Ach reduced in cortex and hippocampus areas[(8.31 ± 2.14) nmol/g] and the activity of ChAT decreased [(3.54 ± 0.42) nkat/L] as well as the activity of AchE increased[(0.21 ± 0.07) nkat/L]. There was significant difference when compared with control group (t = 3.07 - 3.36, P <0.01). Zhinao capsule can reduce the latent period of water maze in rats of AD model, increase the staying rate in bright room, raise the Ach content of cortex and hippocampus and activity of ChAT, reduce the activity of AchE. There was significant difference when compared with model group or control group (t = 2.15-3.34, P <0.05 - 0.01). Conclusion: Zhinao capsule can greatly improve the learning and memory abilities of experimental AD model rats by adjusting the intracerebral cholinergic neurotransmitter.