There is increasing evidence that psychological stress and depression trigger changes in various biochemical parameters in animals and in human subjects. In order to study these effects, the impact of chronic mild stress (CMS) on rats, and of the subsequent administration of Banxia-houpu decoction and fluoxetine, were studied regarding their effects on the following biochemical parameters: 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in various brain regions, natural killer (NK) cell and lymphokine-activated killer (LAK) cell activities in spleen, serum lipid profiles including total cholesterol (TC), high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc) and triglyceride (TG), liver superoxide dismutase (SOD) and nitric oxide synthase (NOS) activities, serum malondialdehyde (MDA), and interleukin-2 (IL-2) levels. The effects of drug administration on preference behavior for consumption of sucrose solution were also assessed. Rats subjected to CMS exhibited a reduction in sucrose intake, 5-HT, 5-HIAA, IL-2, TC, HDLc and LDLc levels, as well as, diminished NK cell and LAK cell activities. Conversely, liver SOD and NOS activities and serum TG and MDA levels were increased following CMS exposures. Administration of Banxia-houpu decoction and fluoxetine produced beneficial effects on the stressed rats by improving sucrose consumption. This behavioral change was accompanied by amelioration of numbers CMS-induced biochemical changes. Banxia-houpu decoction is a traditional Chinese prescription containing pinellia tuber, magnolia bark, hoelen, perilla herb and ginger rhizome, and has been used for centuries in China to treat mental diseases including depression and schizophrenia. However, the pharmacological profile of the decoction is different from that of fluoxetine. These findings suggest that the therapeutic actions of Banxia-houpu decoction are due to a combination of multiple biochemical effects, and may help to elucidate the mechanisms through which distinct biochemical parameters play a role in the etiology of depression.