To evaluate the antidepressant effects of the enzymatic products EP-3 from the total saponins in leaves of Panax notoginseng, a series of animal models and tests, such as the forced swim test (FST), the tail suspension test (TST), learned helplessness procedure, reserpine-induced syndrome, head-twitch test, running and aggressive behaviors were used. EP-3 could shorten the immobility time of FST mice for 43.39% to 52.00% that showed an obvious antidepressant-like effect. EP-3 could significantly reduce the times of escape failures in the model of learned helplessness procedure, which was reduced by 16.56% to 29.96% and 29.63% to 62.82% on day 2 and 4, respectively. EP-3 could significantly reverse the reduction in rectal temperature and the degree of palpebral ptosis, and moderately remit the condition of akinesia induced by reserpine. Moreover, EP-3 could significantly increase the times of head twitches induced by 5-HTP, decrease the times of aggression induced by clonidine and improve the running behavior induced by L-Dopa. However, EP-3 had no effect on the immobility time of TST mice （P>0.05）. In conclusion, EP-3 exerts excellent antidepressant-like effects that maybe have a close relationship with the monoamine neurotransmitters 5-HT, NE, DA or their receptors.