Objective To study the behavior abilities and morphological changes of neurons in the hippocampal CA3 area of Alzheimer's disease (AD) model rats induced by β-myloid protein (Aβ)SUB>1-40/SUB> and observe the effect of melatonin on the AD model rats. Methods A total of 60 Wistar rats were randomly divided into the normal control group，the AD model group and the Melatonin treat group. The AD model rats were established by microinjection of AβSUB>1-40/SUB> solution into right hippocampal CA1 area. Melatonin (10mg/kgI>&#/I>8226;d) was injected into the abdominal cavity in the melatonin treat group for seven days, and an identical volume saline was given for the AD model group and the normal control group. The learning and memory abilities were detected by Y-maze after seven days. Then, the colorimetric method was used to detect the choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity. Caspase-3 and glial fibrillary acidic protein (GFAP) immunopositive cells in the hippocampal CA3 area were observed under a light microscope, and quantitative analysis was performed by cell morphometric technique. The ultramicrostructures of the neurons were observed by transmission electron microscopy (TEM). Results Compared with the AD model group, the learning and memory abilities of the melatonin treat group were obviously improved and the ChAT activity was significantly increased (EM>P/EM><0.05), but the quantity of Caspase-3 and GFAP-immunopositive neurons were decreased (EM>P/EM><0.05). The average absorbance of GFAP-positive cells was significantly decreased (EM>P/EM><0.05). Under TEM, the neurons in the hippocampal CA3 area of the normal control group had moderately electron density, regular nucleus and perinuclear membrane, chromoplasm distributed evenly and abundant cell organelles, but the neurons of the AD model groups were showed shrinkage nucleus, widen perinuclear, aggregated allochromacy and apoptosis changes. The neuronic pathological lesion of the melatonin treat group had lessened than that of the AD model group, some of them had distinct neuronal structure and abundant cell organelles. Conclusion Melatonin could efficiently improve the behavior abilities and decrease the pathological lesion of hippocampus of th