Abstract: To explore the effect of emotional stress on c-fos gene expression of brain areas, two types of animal models of immunomodulation induced by emotional stressor were used. One was footshock apparatus as signal stimuli to cause the rats which were given footshock before emotional stress, the other was empty water bottle to cause the rats which were trained to drink water at two set times each day emotional stress. Both of the emotional stressors were demonstrated to suppress the primary immunity of rats. The c-fos gene, a nuclear proto-oncogene, is transiently expressed in neurons after stimulation and within one hour produces detectable amounts of its product, c-fos. Immunocytochemical localization of the c-fos protein was used to determine neuronal activation in areas of the central nervous system. After two hours of emotional stress, the rats were perfused transcardially, then the brains were removed, blocked, immersed, cut with a freezing microtome, immunocytochemical stained. The results showed that compared to rats in control groups, c-fos protein was strongly expressed at several brain areas in rats of the emotional stressed group. The brain areas contain frontal cortex, cingulum cortex, amygdala, anterior commissure nucleus, arcuate nucleus, diffuse part of dorsalmedial nucleus hypothalamus, solitary nucleus. Conclusion: These brain areas maybe the major central areas activated by the emotional stress

Key words: emotional stress, c-fos gene, brain areas