Li et al.: Onjisaponin B Attenuates Experimental Depression in Mice Depression is a common mental disorder affecting approximately 17 % of the world population. Current therapeutic options are suboptimal due to a lower efficacy and high rates of side effects. Traditional Chinese medicine such as Radix Polygalae has been applied to depressed patients with encouraging outcomes. The main ingredient extracted from Radix Polygalae is onjisaponin B. The aim of this study was to investigate the therapeutic effects of onjisaponin B in experimental depression in mice. 30 male C57/Bl6 mice aged between 6 and 8 w old (25-30 g upon arrival) were purchased from Animal Centre of Shanghai Branch, Chinese Academy of Sciences (Shanghai, China) in this study and inducted to depression mice model. Tail suspension test, forced swimming test, measurement of monoamines and monoamine oxidase methods were used to detect the function of onjisaponin B in depression mice model. Our data showed that in depression mice model, onjisaponin B attenuates the severity of experimental depression. Onjisaponin B inhibits activity of monoamine oxidase A and increases the abundance of 5-hydroxytryptamine and noradrenaline in the brain. These preclinical results indicated the application of onjisaponin B in depressed mice and provided a new potential treatment strategy for patients with clinical depression.