Background Xiaobuxin-Tang, a traditional Chinese herbal prescription recorded in a silk scroll unearthed from Mogao Caves of Dunhuang has been indicated that it can remit depressive disorder. The present study was designed to investigate its antidepressant effects in various animal depression models.Methods Xiaobuxin-Tang was extracted by 70% alcohol, and then three behavioral despair models and 5-Hydroxytryptophan (HTP)-induced head twitch response model were adopted to assess the antidepressant effects of the ethanolic extract of Xiaobuxin-Tang with the study on spontaneous motor activity. Groups of mice and rats received oral treatment with Xiaobuxin-Tang (150-1200 mg/kg) only once acutely in all tests. The duration of immobility was measured during the last 4 minutes of the 6-minutes test period in mice forced swimming test, rats forced swimming test and mice tail suspension test. In 5-HTP-induced head twitch response, the mice were intraperitoneally administered with 120 mg/kg of L-5-HTP, and then the cumulative number of head twitches was counted in 20 minutes. Spontaneous motor activities of mice were recorded automatically in 10 minutes by VIDEOMEX-V image analyticsystem.Results The extract at doses of 300 mg/kg (p.o.) and 600 mg/kg (p.o.) significantly decreased the duration of immobility time in a dose dependent manner in mice forced swimming test; also, the extract at dose of 1200 mg/kg (p.o.)significantly decreased the duration of immobility time in rat forced swimming test. Furthermore, the extract at a dose of 600 mg/kg had the same effect in mice tail suspension test. Meanwhile, the extract at the effective doses for behavioral despair models, had no effect on spontaneous motor activity in mice. The extract (300-1200 mg/kg, p.o.) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20 minutes.Conclusion Our results suggested that the ethanolic extract of Xiaobuxin-Tang exerts antidepressant-like effect.