Objective To analyze the correlation of cognitive function with the expression of Arc protein and amyloid-beta peptide (Aβ) in the hippocampus of diabetic rats, and to assess the role of synaptic plasticity in the possible pathogenesis of diabetic encephalopathy (DE). Methods Thirty male SPF SD rats (8 weeks old) were randomly assigned to diabetes mellitus (DM) group and control group. After 4 weeks of high fat diet feeding, the rats of DM group were injected intraperitoneally with streptozotocin at a dose of 30mg/kg to establish diabetic model. Body mass, fasting blood glucose (FBG), and fasting serum insulin (FSI) were monitored at several stages, and insulin sensitivity index (ISI) was calculated. At the end of the experiment, water maze test was carried out to evaluate the cognition of all the rats. The expression of Arc and Aβ in the hippocampus was detected and observed by ELISA, immunohistochemistry and Western blotting. Results The DM group spent shorter time in the target quadrant (P＜0.01) and lower frequency of crossing the original platform site (P＜0.01) than the control group. The expression level of Aβ was obviously higher, while that of Arc/Arg3.1 significantly lower in the DM group than in the control group (P＜0.01). Conclusion The cognitive impairment in diabetic rats is possibly related to the decreased Arc expression-induced synaptic plasticity imbalances, and further increased Aβ deposition and neuronal damage.