Objective To determine the effect of aspirin on the spatial learning and memory abilities and the hippocampal expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-10 (IL-10) in the rat model of Alzheimer’s disease (AD), and to elucidate its potential anti-inflammatory effect in the prevention and treatment of AD. Methods A total of 40 SD rats were randomly divided into 4 groups:control group, AD model group, and low- and high-dose aspirin groups (n=10). Distilled water was used to feed the rats from the 2 former groups, and 1 mg/ml and 2 mg/ml aspirin were given to the 2 latter groups respectively for 3 weeks. Then the rat model of AD was established by injecting Aβ25-35 into the lateral cerebral ventricle, and then all were fed continuously for another 3 weeks. The spatial learning and memory abilities of the rats was tested by Morris water maze. Then the rats were sacrificed and the hippocampal tissues were collected to detect the levels of IL-1β, TNF-α, IL-4 and IL-10 by enzyme linked immunosorbent assay (ELISA). Results The mean escape latency was significantly shorter in the high-dose aspirin group at the 1st, 2nd and 3rd days and in the low-dose group at the 3rd day when compared with the model group (P＜0.05). The expression levels of IL-1β and TNF-α were significantly increased (P<0.001), but those of IL-4 and IL-10 were obviously decreased (P<0.05) in the model group than the control group. The low-dose group also had notably higher TNF-α and lower IL-4 levels when compared with the control group (both P<0.01). High-dose aspirin treatment resulted in obvious decreases of the IL-1β and TNF-α levels (P<0.01) and increases of those of IL-4 and IL-10 (P<0.05) than the AD group. However, low dose of aspirin only decreased IL-1β level (P<0.01). Conclusion Aspirin intervention promotes the spatial learning and memory abilities in AD rats. It exerts protective effect in the pathogenesis of AD and inhibits the development of inflammatory response through inhibiting glial activation and improving the balance of pro- and anti-inflammatory cytokines.