〔Abstract〕 Objective To investigate the effect of high-fat diet on hippocampal morphological changes and synapse-related protein Synapsin-1(Syn-1) expression in rats. Methods 18 male SD rats were randomly divided into a control group and a model group, with 8 rats in the control group and 10 rats in the model group. Rats in the model group were given high-fat diet lasting for 4 weeks, and rats in the control group were given standard control diet. The changes of blood lipid in the rats of the two groups were detected, the morphological changes of the hippocampal tissues were observed by hematoxylin-eosin(HE) staining and silver staining, and the mRNA and protein expression of Syn-1 in the hippocampus was detected via real-time fluorescent quantitative PCR(qRT-PCR) and immunohistochemistry technique,respectively. Results Compared with those in the control group,the serum levels of total cholesterol( TC),low density lipoprotein cholesterol( LDL-C),and high density lipoprotein( HDL) in the model group significantly increased,and the level of leptin significantly reduced( P<0. 01). Results of HE staining showed that the neurons in the DG,CA3 and CA1 regions of model rats were irregular in shape,loosely arranged,and hyperchromatic in nuclei. Consistently,the neurons in DG,CA3 and CA1 regions of the model rats were also hyperchromatic via silver staining. Compared with that in the hippocampus of control rats,the mRNA and protein expression of Syn-1 in the model group was significantly lower. Conclusion High-fat diet can induce hyperlipidemia,hippocampal neuron damage,and decrease expression of synaptic binding protein Syn-1 in the hippocampus of rats.