Objective To Study the depression-like behavior and impairment of learning and memory induced by chronic injection of corticosterone in mice. Methods Forty male C57BL/6J mice were divided into four groups, the control group, and the corticosterone groups (20, 40, 80 mg/ kg). The mice received subcutaneous injection of corticosterone once a day for 21 days. The depression-like behaviors were detected by open field test ( OFT), tail suspension test (TST) and forced swimming test (FST). To select the most effective dose of corticosterone, TST, FST, object location recognition test, and Morris water maze (MWM) test were used to study the corticosterone-induced depression-like behaviors and impairment of learning and memory in the mice. Results Compared with the control group, the movement distance and duration were significantly decreased in the corticosterone injection groups (40, 80 mg/ kg) ( P < 0.01 or P < 0.05). In the TST group, the immobilization time was significantly increased in the corticosterone injection group (40, 80 mg/ kg) ( P < 0.05). The TST and FST showed that the immobilization time of the corticosterone injection group (40 mg/ kg) was significantly increased ( P < 0.05). The object recognition test showed that the discrimination indexes of the object location recognition were decreased in the corticosterone injection group (40 mg/ kg). The MWM test showed that the escape latency was increased ( P <0 . 05), and the number of crossing in target quadrant and the velocity in target quadrant were decreased ( P < 0.05) in the corticosterone injection group (40 mg/ kg). Conclusions Chronic injection of corticosterone can induce depression accompanied with learning and memory impairment in mice.