Objective: To study the antidepressant effects and its mechanism of bioactive compounds (metabolite extract) from entomogenous fungi (BCEF) on experimental animal models of depression. Methods: The antidepressant effect of BCEF was examined on the acquired models of depression (rats and mice in forced swimming test) and unpredictable chronic stress mouse models. The behavior alterations were assayed by detecting the duration of immobility in forced swimming test. UV spectrophotometer analysis technique was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in mice brain mitochondria; and colorimetric method was used to detect the content of malondealdehyde (MDA), nitrogen oxide (NO) in rat brain cytoplasm and mitochondria. Results: BCEF (25, 50,100 mg/kg) could obviously shorten the immobility time in forced swimming mice and BCEF (50,100 mg/kg)could obviously shorten the immobility time in forced swimming rats. Both of them showed some extent of dose-effect relationship. BCEF (50, 100 mg/kg) could significantly inhibit the increase of MDA and NO content in brain mitochondria and cytoplasm in chronic unpredictable stress models. BCEF (25,50,100 mg/kg)could obviously enhance the activities of SOD and GSH-PX. BCEF (50 mg/kg) also enhances the activities of CAT. Conclusion: BCEF has antidepressant effects in depressed animal models. The anti-oxidation may be one of the important mechanisms.