Abstract: AIM To investigate the role of brain-gut peptides in the electro-acupuncture regulated neuroendocrine-immune network as well as its mechanism. METHODS The rats were randomized into 5 groups, including the control, the Tsusanli, the immunosuppressive model, the non-acupoint group, and the Tsusanli+immunosuppressive groups. The Tsusanli group rats, fixed, were electro-acupunctured at Tsusanli (He-Sea Point, St 36) on both sides continually for 30 min at any point between 07:00 and 09:00 for 7 d on a daily basis. The location of the acupoints for EA: Tsusanli (He-Sea Point, St 36) was identified at approximately 5 mm below the small end of the fibula on the outer lower side of knee joint hind limb of the rats and the non-acupoint was 0.5 cm beyond Tsusanli. Changes in substance P (SP) and vasoactive intestinal peptide (VIP) contents in the pituitary gland and peripheral blood were determined by radioimmunoassay. T-lymphocytic subgroups were assayed to reflect the cellular immunity. Erythrocytic immunity was assayed by red blood cell C3b receptor rosette (RBC-C3bRR) and red blood cell immune complexes rosette (RBC-ICR). RESULTS After EA, the immuno-adhesiveness of T-lymphocytic subgroups and erythrocytes of both healthy rats and immuno-suppressive rats was enhanced. What is more, the values of SP and VIP in rat pituitary gland and peripheral blood increased significantly in comparison with that of the control and were positively correlated with the change in CD4+. There was no significant difference between the indexes of the non-acupoint group and that of the control. CONCLUSION EA at Tsusanli can positively regulate the T-lymphocytic immunity and erythrocytic immuno-adhesiveness in the peripheral blood of both normal and immuno-suppressive groups of rats. When the immune system is regulated by EA at Tsusanli, the contents of SP and VIP in the central and peripheral blood are positively correlated with the change in the immune system, indicating that SP and VIP have an important role in the EA regulation of the neuroendocrine-immune network. The results of our study, consistent with previous findings in the field, make an important complement to the regulatory effects of EA on the immune system.