Objective To investigate whether there is preventive and treatment effect of aspirin on the rat model of Alzheimer’s disease (AD) and its influence on the expression of interleukin (IL)-6, IL-1β and tumor necrosis factorα(TNFα) in the models. Methods A total of 50 SD rats were randomly divided into 5 groups: control group, model group, and low-, middle- and high-dosed aspirin groups. After fed with normal saline containing aspirin at 0, 0.5, 1 and 2g/L respectively for the later 4 groups for 3 weeks, the rats model of AD was established by injecting 5 μl amyloid-beta protein 25?35 (Aβ25-35) into the lateral cerebral ventricle followed by another 3 weeks’ aspirin treatment, while those of control was given normal saline at same volume. The escape latency of the rats was tested in Morris water maze, and the levels of IL-6, IL-1β, TNFα in the brain were detected by enzyme linked immunosorbent assay (ELISA). Results The mean escape latency was significantly shorter in the high-, middle- and low-dosed aspirin groups than in the control group. The brain levels of IL-1β was the highest in the model group, the lowest in the control group, and in a decreasing order in the low-, middle- and high-dosed aspirin groups, with significant difference among them. The brain level of IL-6 was in a similar trend as that of IL-1β in the 5 groups, but there was no significant difference among them. The level of TNFα was also the highest in the model group, and the lowest in the control group, and those in the other 3 groups were between the 2 values. Among the 3 aspirin groups, the middle-dosed group had the highest level of TNFα, and the low-dose group had the lowest level, with significant difference between the 2 groups. Conclusion Lateral cerebral ventricle injection of Aβ25-35 causes short-term decrease in learning and memory abilities in rats. Aspirin intervention attenuates the induced decrease in the abilities. It might exert the protective effect on the learning and memory abilities through down-regulating IL-1β, IL-6, and TNFα in the brain.