Objective Amyloid β protein (Aβ) has been thought to be responsible for loss of memory in Alzheimers disease (AD).Rattin (RN), a Humanin-like peptide with 38 amino acids (14 residues longer than Humanin), shared with Humanin the ability to protect neurons against Aβ toxicity.However, it is unclear whether RN can protect against Aβ-induced deficits in cognitive function.Methods The present study observed the effects of intrahippocampal injection of RN on spatial learning and memory of rats in the Morais water maze test and tried to explore the potential protective function by which RN against Aβ31-35-induced neurotoxicity in spatial learning and memory.Results (1) intrahippocampal injection of 5 nmol Aβ31-35 revealed a significant decline in spatial learning and memory; (2) both Hidden platform test and Probe trial, pretreatment with RN (0.02 nmol, 0.2 nmol, 2 nmol) markedly improved and effectively reversed the impairment in spatial learning and memory induced by Aβ31-35 in a dose dependent manner; and (3) none of the drugs, including Aβ31-35 and different concentrations of RN, affected the vision and swimming speed of the rats.Conclusion These findings indicated that Aβ31-35 significantly impaired spatial learning and memory of rats, while RN enhanced basal memory function and effectively prevented the behavioral impairment induced by neurotoxic Aβ31-35.Thus, the present study provided a direct behavioral evidence that RN could protect against Aβ-induced deficits in cognitive function, suggesting that up-regulation of central Humanin-like peptide might be beneficial in the prevention and treatment of AD.