Abstract: OBJECTIVE This study aimed to investigate the effect and possible impact mechanism of Astragaloside Ⅳ on memory deficit of lipopolysaccharide (LPS) induced Alzheimer’s disease model mice. METHODS The AD model was established by intracerebroventricular injection of LPS. Different doses of Astragaloside Ⅳ (80， 40， or 20 mg/kg) were orally administered once a day. 14 days after the LPS injection， behavioral experiments including Morris water maze test and novel object recognition (NOR) test were performed to exam mice’s learning and memory abilities. 21 days after the LPS injection， the levels of TNF-α、IL-1β in hippocampus were evaluated by ELISA. The morphology and number of microglial cells were assessed by Iba-1 immunohistochemistry experiment. RESULTS Results of behavioral experiments showed that LPS injection could significantly impair cognitive function of AD mice， and Astragaloside Ⅳ administration could remarkably relieve the impairment. The levels of TNF-α and IL-1β were increased after LPS injection， while Astragaloside Ⅳ could remarkably reduce the concentrations of these inflammatory factors. Furthermore， Iba-1 immunostaining for microglia revealed that the activation of microglia induced by LPS were significantly inhibited by Astragaloside Ⅳ CONCLUSION These results indicate that Astragaloside Ⅳ could ameliorate learning and memory impairment induced by LPS and this effect was found to be mediated through inhibition of microglial activation and neuroinflammation.