Objective To explore the antidepressant mechanism of Shenwei Ningyu tablets on animal models induced by three drugs. Methods Three drug-induced animal models were established, following 1 week of drug administration. For the experiment aimed at strengthening the effect of monoamine, the animals in each group were injected with pargyline hydrochloride by intraperitoneal injection, followed by a tail vein injection of 5-hydroxytryptamine acid. The frequency of head-shaking within 25 min was observed. For the inhibition of norepinephrine ( NE) reabsorption test, mortality was counted in each group following subcutaneous injection of NE. In the monoamine oxidase (MAO) inhibition test, tryptamine hydrochloride was injected into the tail vein of the animals in each administration group, and the “pedal” movement of each rat was observed. Results For the enhanced monoamine action test, the frequency of head-shaking in mice in each administration group was significantly higher than that in the model group. For the inhibition of NE reabsorption assay, compared with the model group, the mortality of mice in each administration group was significantly higher, and there was a significant difference between the low-dose and model groups (P<0.05). For the MAO inhibition test, obvious “pedaling” movements were observed in the model group, and the number of “ pedaling” movements after after animal modeling in each administration group was significantly higher than that in the model group; however, the difference was not significant. Conclusions The antidepressant effect of Shenwei Ningyu tablets may be related to its efficacy in enhancing NE nerve function and 5-hydroxytryptamine(5-HT).