β-amyloid (Aβ) deposition is considered to be partly responsible for cognitive dysfunction in Alzheimers disease (AD).Down-regulation of c-AMP responsive element-binding protein (CREB) has been linked to the synaptic deficits after Aβ elevation.And silent information regulator two proteins 1 (SIRT1) is essential for normal cognitive function, and modulates memory formation via post-transcriptional regulation of CREB expression.Here, we report that resveratrol, a SIRT1 activator, significantly inhibits the impairment of spatial learning and memory function and the attenuation of LTP in CA1 induced by hippocampal injection of Aβ1-42 in rat.Interestingly, we also show that resveratrol significantly prevents the reduction of SIRT1 and CREB phosphorylation induced by Aβ1-42 in rat hippocampus.Taken together, our results demonstrate that resveratrol can protect neurons against Aβ1-42-induced dysfunction of the spatial learning and memory function and the hippocampal LTP in rats, and the potential mechanisms maybe involved in the reversion of the reduction of SIRT1and CREB phosphorylation induced by Aβ1-42.