Objective To investigate the effect of chronic corticosterone administration on depressive-like behaviour and synapsin-1 expression in mice. Methods C57BL/6J mice were randomly separated into 2 groups (n=10 per group): control and Corticosterone (CORT). CORT was dissolved in vehicle (0.45%hydroxypropy-β-cyclodextrin, β-CD). Corticosterone (5mg/kg/day) was delivered for 35 days in drinking water and continued when the behavioral tests were performed. Control animals received vehicle(β-CD) in drinking water during the entire experiment. The behavior tests were applied to evaluate depressive-like behavior of the model. Results The sucrose preference test showed no significant difference in sucrose intake between control and CORT group (P > 0.05). The immobility time was increased in the forced swim test (P < 0.05). The cumulative duration,distance moved and frequency in the center area were decreased in the open field test(P < 0.05,P < 0.01,P < 0.01). The cumulative duration in the border area was increased(P < 0.01). Latency to food was decreased in the novelty suppressed test(P < 0.05). Immunohistochemisty analysis showed a notably decreased expression of Syn-1 in the hippocampus CA1,CA3 and DG. Conclusions Chronic administration of CORT induced depressive-like behavior and decreased Syn-1 expression.