Abstract: Objective To investigate the effects of medium-chain fatty acid (MCFA) and α-linolenic acid (ALA) on learning and memory behavior of APP/PS1 transgenic mice and expression levels of Aβ42, Tau protein in their brains. Methods Twentyif ve APP/PS1 transgenic mice, aged 4 weeks, were randomly divided into ALA+MCFA group (combined intervention group, n=8), MCFA group (intervention group, n=9) and long chain fatty acid (LCFA) group (control group, n=8) according to their fasting body weight, and another 10 wild type mice (WT) served as normal control group. The mice were fed diets with different fatty acid formulas for 36 weeks. Then Morris water maze was used to perform place navigation test and spatial probe test, meanwhile the average escape latency, time across the platform and time percent during platform quadrant were recorded. Immunohistochemical assay was used to detect Aβ deposition in hippocampus, and the APP, Aβ42 and Tau protein levels were detected by western blot. Results Compared with LCFA group, the average escape latency of Morris water maze place navigation test in ALA+MCFA and MCFA group reduced significantly (P< 0.05), and the time across the platform on probe day was significantly greater (P< 0.05), Aβ plaques in hippocampus were relatively less, and the level of Aβ 42 and Tau protein in cortex and hippocampus were relatively lower (P< 0.05). Conclusion ALA and MCFA can improve the learning and memory function of the APP/PS1 transgenic mice by reducing the production of Aβ42 protein and the phosphorylation of Tau protein, therefore they may have the potential to delay the development and progress of Alzheimer's disease.