This study was designed to investigate whether icariside Ⅱ (ICS Ⅱ) could ameliorate spatial learning and memory impairment in rats induced by streptozotocin (STZ).Methods: Male Sprague-Dawley rats were randomly divided to 4 groups : sham group (n =14), model group (n =12) ,ICS Ⅱ low dose group (n =12) ,ICS Ⅱ high dose group(n =11).Model group rats were injected with STZ 5 μL(1.5 mg / kg) into the bilateral lateral.Low and high dose groups were administered by ICS Ⅱ at doses of 3,10 mg/kg on 2th day after STZ for 21 days, while sham and model groups were done with volume-matched vehicle,instead.Morris water maze was used to examine the learning and memory ability on 16th day.Nissl staining were performed to observe neuronal morphology in hippocampus.Western blot assay was used to detect the protein levels of hippocampal beta-amyloid (Aβ1-40 and Aβ1-42), amyloid precursor protein (APP), β-site APP cleavage enzyme (BACE1), insulin-degrading enzyme (IDE), neprilysin (NEP), inflammatory mediators such as tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), cyclooxygenase-2 (COX-2).Results: Studies found that the mean escape latency was dramatically increased in model group rats;Morever, the hippocampal neurons were degenerated and damaged seriously, the density of hippocampal neurons were decreased in model group rats; Protein levels of Aβ1-40 ,Aβ1-42,APP,BACE1 were significantly increased , but NEP was decreased,IDE was not change in model group rats; Inflammatory mediators such as TNF-α, IL-1β, COX-2 protein levels were significantly increased in model group rats.However, ICS Ⅱ high dose group clearly reversed these changes.Conclusion: Under the experimental conditions, ICS Ⅱ can significantly ameliorate spatial learning and memory impairment induced by STZ in rats.The possible mechanism,at least in part,is due to reducing Aβ levels and inhibiting inflammatory mediators such as TNF-α,IL-1β ,COX-2protein levels.