To study the rules of protein expression of proto-oncogene (c-Fos/c-Jun) in different brain areas and nucleus of psychological stressed mice and the regulatory effect of modified Xiaoyao Pill (SXP).The mouse psychological stress model was established by electrical stimulation; SXP was administrated at the dose of 2 mg/g; the protein expression of c-Fos and c-Jun in different brain areas and nucleus, including hippocampus (CA1-4), central amygdaloid nucleus (CAN), paraventricular nucleus (PVN) and supraoptic nucleus (SON), were detected by immunohistochemical method.The protein expressions of c-Fos and c-Jun in all the tested brain areas of model mice 3 h after being stressed for 1, 3 or 5 times, were significantly higher than those of the normal mice (P < 0.01); After being stressed for one time, the expression at 1 h after stimulation was lower than that at 3 h after stimulation (P < 0.05), the expression in mice treated with SXP was lower than that in the untreated group, 3 h after three or five times of stress (P < 0.05 or P < 0.01).The protein expression of c-Fos and c-Jun began to rise 1 h after psychological stress and reached the peak at the 3rd h. That of c-Fos dropped to the normal level approximately after 6 h, but the dropping did not happen in expression of c-Jun, it remained on the high level unweakened after repeated stimulation; SXP can remarkably down-regulate the proto-oncogene (c-Fos and c-Jun) expressions after psychological stress in mice.