Based on the report of previous clinical study which showed cholinergic receptor antagonist scopolamine had antidepressant activity, this study was to investigate the antidepressant activity of scopolamine and explore its effective dose in mice, and to evaluate the effect of scopolamine on the central nervous system and learning/memory ability at its antidepressant effective dose.  Tail suspension test, forced swimming test, step-down passive avoidance test and open field test were used to evaluate its effects on mice.  Compared with the vehicle control group, single-dose administration of scopolamine (0.1−0.4 mg·kg⁻¹, ip) significantly decreased the immobility time (P < 0.01 or P < 0.001) in tail suspension test, and significantly decreased the immobility time (P < 0.001) in forced swimming test, but had no effect on the step-down latency and errors in step-down passive avoidance test.  Scopolamine (0.1 and 0.2 mg·kg⁻¹, ip) had no influence on the locomotor activity in open field test, while at dose of 0.4 mg·kg⁻¹ significantly increase the locomotor activity.  These results showed that scopolamine produced reliable antidepressant effect at doses of 0.1 and 0.2 mg·kg⁻¹, without impairment on learning and memory, as well as excitory or inhibitory effect on central nervous system in mice.