According to Traditional Chinese Medicine (TCM), the liver is the origin or most associated with stress related disorders such as depression. Sinisan, a TCM prescription, has been used as a hepatic protectant. We examined whether Sinisan exerts therapeutic effects in an experimental animal model: the chronic restraint stress (CRS) model. Sinisan was administered in the animal's drinking water at a concentration of 100mg/kg for 21 days (7 days pre-CRS and 14 days during the CRS). Spatial learning and memory were measured 24h after the CRS procedures using the Morris Water Maze (MWM). Aggressive behavior and body weight were determined as well. The Sinisan treatment decreased aggressive behaviors and reversed CRS-induced impairment of spatial learning and memory as well as decreased rate of growth. In conclusion, our results suggest that Sinisan does exert measurable therapeutic effects in an experimental chronic stress model.