This study investigated the antidepressant activity of ethanolic extract of U. lanosa Wallich var. appendiculata Ridsd (UL(EtOH)) for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of UL(EtOH) in FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the UL(EtOH). The results showed that UL(EtOH) exhibited antidepressant-like activity in FST and TST in mice. UL(EtOH) increased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of UL(EtOH). UL(EtOH) inhibited the activity of MAO-A. The amount of RHY in UL(EtOH) was 17.12 mg/g extract. Our findings support the view that UL(EtOH) exerts antidepressant-like activity. The antidepressant-like mechanism of UL(EtOH) may be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice.