Rattin (RN), a humanin-like peptide, shared with Humanin ability to protect neurons against amyloid β protein (Aβ)-induced cellular toxicity.However, it is unclear whether RN can prevent Aβ-induced deficits in synaptic plasticity and cognitive function.The present study, by using Morris water maze (MWM) and electrophysiological techniques, investigated the effects of intrahippocampal injection of RN on the hippocampal Long-term potentiation (LTP) and spatial learning and memory of rats.The results showed: (1) Aβ25-35 (5 nmol)injection did not affect the baseline synaptic transmission, but significantly suppressed high frequency stimulation (HFS)-induced LTP in hippocampal CA1 region;(2) RN (1 nmol) administration alone did not affect the baseline synaptic transmission and the maintenance of LTP;(3) pretreatment with RN (0.1, 1 nmol) effectively prevented Aβ25-35-induced LTP deficit;(4) intrahippocampal injection of 5 nmol Aβ25-35 resulted in a significant decline in spatial memory of rats in MWM test;(5) RN (1 nmol) administration alone did not affect spatial learning and memory, while RN (0.1, 1 nmol) pretreatment effectively reversed the impairment of spatial learning and memory induced by Aβ25-35.Thus, these findings in the present study suggests that up-regulation of central humanin-like peptide might be beneficial in the prevention and treatment of cognitive deficits seen in the Alzheimers disease.