Objective To explore the effect of autophagy on the expression of synaptophysin (Syn) and postsynaptic density material 95 (PSD-95) in CA1 hippocampal region of vascular dementia rats. Methods A total of 96 healthy male SD rats were randomly divided into sham operation group (Sham group), vascular dementia model group (VD group), autophagy inhibitor 3-methyl adenine preconditioning group (3-MA group) and autophagy agonist rapamycin preconditioning group (Rap group). Each group was further randomized into 4 subgroups 1, 2, 4 and 8 weeks after model establishment. The rat model of vascular dementia was established using a modified Pulsinelli four-vessel occlusion method. The expressions of Syn and PSD-95 in CA1 hippocampal region of the vascular dementia rats were detected by Western blotting analysis. Results (1) Compared with the Sham group, the ratio of LC3-Ⅱ/LC3-Ⅰ in CA1 hippocampal region of the vascular dementia rats was significantly increased and the expressions of Syn and PSD-95 were significantly decreased in VD group at different time points (all P<0.01). Compared with the VD group, the ratio of LC3-Ⅱ/LC3-Ⅰ was significantly decreased and the expressions of Syn and PSD-95 were significantly increased in 3-MA group at different time points (P<0.05 or P<0.01); the ratio of LC3-Ⅱ/LC3-Ⅰ was significantly increased and the expression of Syn and PSD-95 were significantly decreased in Rap group at different time points (all P<0.01). (2) Correlation analysis showed that the ratio of LC3-Ⅱ/LC3-Ⅰ was negatively correlated with Syn and PSD-95 expression (all P<0.01). Conclusion Autophagy may inhibit the expression of synaptic plasticity related proteins, Syn and PSD-95, in CA1 hippocampal region of the vascular dementia rats, and suppressing autophagic activity is benefitial to the synaptic plasticity.