A rat model of depression has been recently developed by exogenous corticosterone administration. In this study, we further determined whether corticosterone administration also increased depression-like behavior in mice and explored the brain biochemical consequences of exposure to this administration paradigm. Mice received repeated injections of vehicle and 20 mg/kg of corticosterone for 1, 3 and 5 weeks, and then were subjected to the forced-swim and tail suspension tests. The results showed that repeated corticosterone injections increased immobility behavior in the forced-swim and tail suspension tests in a time-dependent manner. Meanwhile, this injection paradigm produced a time-related effect on tyrosine hydroxylase (TH) levels in the hippocampus of mice. These results are consistent with correlations in stress-induced depression models, and suggest that the repeated corticosterone injection paradigm provides a useful and reliable mouse model within which to further study the role of stress and glucocorticoids in depressive illness, as well as screen for antidepressants or preventive drugs.