To investigate improvement of melatonm on leammg and memory impairment induced by amyloid β- peptide 25-35 (Aβ25-35) in elder rats. METHODS: Step-down type passive avoidance test, shuttle-box test, and Morris water maze were used together to determine effects of Aβ25-35 and melatonin on learning and memory. Pathological changes were observed by HE, Congo red, and Ag staining. RESULTS: The elder rats were injected bilaterally Aβ25-35 20 g into the hippocampus to induce learning and memory dysfunction. Melatonin administration (0.1, 1, and 10mg/kg, ig×8 d) to the Aβ25-35-treated rats prolonged the latency, shortened the total stimulating time, and decreased the number of errors in the step-down test. Suttle-box test showed that melatonin improved amnesic rats" performace at the same doses. Melatonin (0.1, 1, and 10mg/kg), giving for 10 d, could enhance the spatial resolution of amnesic rats in Morris water maze test. Also in Aβ25-35-treated group, a decrease in the number of neurons in cortex and hippocampus, a massive glial reaction, and neurophilic phenomenon were detected by HE staining; the positive vascular amyloidosis by Congo red and fibrils by Ag staining were observed. Melatonin (0.1 and 1 mg/kg)could inhibit above pathological changes in Aβ25-35-group. CONCLUSION: Melatonin improved the impaired learning and memory induced by Aβ25-35 in elder rats.