Some researchers focus on research of the nature of syndromes. The methods of combining traditional Chinese medicine syndrome and diseases and the correspondence between formulas and syndromes may be used in research of the nature of syndromes. According to combined theories of zang-organ state and seven emotions in traditional Chinese medicine with stress theory in modern medicine, the authors applied the methods of chronic immobilization stress to induce liver depression and spleen deficiency syndrome in rats based on the thinking of relativity on formula and syndrome. The research showed that the central neurobiology mechanism of liver depression and spleen deficiency syndrome closely correlates to the hypothalamic-pituitary-adrenal axis, brain-gut axis, myriad central neurotrophic factors, neurotransmitters, neuropeptides and hormones and their receptors, involving in many encephalic regions such as the hypothalamus, hippocampus, cortex, amygdale, etc. The authors will combine their previous work with multi-disciplinary research, such as genomics, proteomics, metabolomics and bioinformatics in future studies, to reveal the scientific connotations of liver depression and spleen deficiency syndrome.