Objective To observe the effect of TCM compound of resolving stagnation for tranquilization ( RST) on neurotransmitters and brain derived neurotrophic factors ( BNDF ) in depression rat model induced by chronic unpredictable stress ( CUS) , and to reveal the mechanism of RST on the treatment of depression.Methods Altogether 60 male SD rats were randomly divided into normal group, model group, high-, mid-and low-dose RST groups at dosage of 8.2, 16.3, 32.7 g/kg, and fluoxetine group with dose of 10 mg/kg.The rats of four therapy groups were administered intragastrically drugs with undergoing CUS for consecutive thirty-five days.The behavioral changes of rats were observed by open field test and novelty-suppressed feeding-test.The content of dopamine ( DA) , 5-hydroxeytryptamine(5-HT) , 5-hydroxyindole acetic acid (5-HIAA) and norepi-nephrine( NE) in hippocampus and cortex were determined by HPLC.And the expression of BDNF in hippocampus was measured by Western blot.Results Compared with the normal group, the rats ’ weight increased slowlier and the spontaneous activity decreased in model group; the contents of 5-HT and NE in cortex and the content of 5-HT, 5-HIAA and NE in hippocampus significantly reduced ( P<0.05 ).Compared with the model group, the spontaneous activity significantly increased in all therapy groups;the contents of 5-HT and NE in cortex dramatically increased in fluoxetine group and mid-, high-dose group ( P<0.05 );the contents of 5-HT and 5-HIAA in hippocampus significantly increased in all three RST groups ( P<0.05 ); the content of NE in hippocampus significantly increased in low-and high-dose group ( P<0.05 ).The expression of BDNF in hippocampus significantly increased in fluoxetine group and high-dose RST group ( P<0.05).Conclusion The anti-depression mechanism of TCM compound formulated by principle of resolving stagnation for tranquilization may be related to the effects of increasing neurotransmitters and up-regulation of BDNF.