Abstract: OBJECTIVE To explore the efficacy and mechanism of levetiracetam in the treatment of Alzheimer's disease from the perspective of oxidative stress and neuroinflammation. METHODS Amyloid precursor protein-swe/presenilin-1- 1dE9(APP/PS1) model mice were injected with different doses of levetiracetam(5, 10, 20 mg·kg^-1) through tail vein every two days for a total 30 consecutive days. The locomotor activity experiment was used to investigate the locomotor ability of APP/PS1 mice. Morris water maze experiment was used to investigate the spatialcognitive ability of APP/PS1 mice. Immunohistochemistry experiment was used to evaluate the degree of microglia activation in hippocampus of APP/PS1 mice. Caspase-1 activity of hippocampus in APP/PS1 mice was tested by kit. The expressionlevel of caspase-1 was detected by Western blotting. The expression levels of interleukin(IL)-1β, NOD-, LRR- and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC) and caspase-1 activityin hippocampus were detected by colorimetric assay. The superoxide dismutase(SOD) activity, glutathione(GSH) level, H₂O₂ level and malondialdehyde(MDA) level in hippocampus were detected by colorimetric kit. RESULTS Compared with control group, the escape latency in Morris water maze and the activation degree of microglia in hippocampus was significantly increased, and the protein level of IL-1β, NLRP3 and caspase-1 was obviously increased in APP/PS1 group. In addition, the SOD activity and GSH level was significantly reduced with MDA level increased in APP/PS1 model group. Compared with APP/PS1 group, levetiracetam 10 mg·kg^-1 and 20 mg·kg^-1 significantly reduced the escape latency and microglia activation, and obviously decreased the protein level of IL-1β, NLRP3 and caspase-1, significantly enhanced SOD activity and elevated GSH level while decreased MDA level. CONCLUSION Levetiracetam can significantly improve the cognitive function of APP/PS1. Its mechanism may be related to inhibiting the NLRP3 inflammasome activation and oxidative stress.