Abstract: Objective To explore influence of vagus nerve on multiple organ function and immune reaction of T lymphocytes in septic rats. Methods Forty Sprague-Dawley rats were divided into sham injury group, sepsis group, vagus nerve stimulation (VNS) group, and vagotomy (VGX) group, according to the random number table, with 10 rats in each group. Rats in sepsis group, VNS group, and VGX group were inflicted with sepsis by cecal ligation and puncture (CLP). Rats in VNS group were given electrical stimulation on left cervical vagus nerve for 15 min right after CLP. Rats in VGX group underwent vagotomy of left cervical vagus nerve at 30 min before CLP. At 24 h after CLP, serum of rats was collected to detect levels of alanine transaminase (ALT), aspartate aminotransferase (AST), glycocholic acid (CG), creatine kinase (CK), myocardial creatine kinase (CK-MB), blood urea nitrogen (BUN), and serum creatinine by fully automatic biochemistry analyzer. The left lung of rats was collected to determine wet or dry mass, and wet to dry (W/D) ratio was calculated. The right lung of rats was collected to measure the activity of pulmonary myeloperoxidase (MPO) by enzyme linked immunosorbent assay (ELISA). Spleen of rats was collected to determine the proliferative activity of CD4⁺ T lymphocytes by cell counting kit 8, and real-time fluorescence quantitative polymerase chain reaction and ELISA were used to quantify mRNA expressions and levels of interleukin 2 (IL-2), interferon-γ, and IL-4, respectively. Data were processed with one-way analysis of variance and Tukey′s honest significant difference test. Results (1) The levels of serum ALT, AST, CG, CK, CK-MB, BUN, and creatinine, pulmonary W/D ratio, as well as MPO activity of rats in sepsis group were significantly higher than those in sham injury group and VNS group (P<0.01) and were significantly lower than those in VGX group (P<0.01). (2) The proliferative activity of CD4⁺ T lymphocytes of rats in sepsis group was 0.93±0.03, which was significantly lower than 1.54±0.07 of rats in sham injury group (P<0.01). The proliferative activity of CD4⁺ T lymphocytes of rats in VNS group was 1.15±0.15, which was significantly higher than that of rats in sepsis group (P<0.01). The proliferative activity of CD4⁺ T lymphocytes of rats in VGX group was 0.75±0.06, which was obviously lower than that of rats in sepsis group (P<0.01). (3) In comparison with those of rats in sham injury group, the levels of IL-2 and interferon-γ in CD4⁺ T lymphocytes of rats in sepsis group were markedly decreased (P<0.01), while the level of IL-4 was significantly increased (P<0.01). In comparison with those of rats in sepsis group, the levels of IL-2 and interferon-γ in CD4⁺ T lymphocytes of rats in VNS group were obviously increased (P<0.01), while the level of IL-4 was markedly decreased (P<0.01). As compared with those of rats in sepsis group, the levels of IL-2 and interferon-γ in CD4⁺ T lymphocytes of rats in VGX group were markedly decreased (P<0.01), while the level of IL-4 was significantly increased (P<0.01). (4) As compared with those of rats in sham injury group, expressions of IL-2 and interferon-γ mRNA in CD4⁺ T lymphocytes of rats in sepsis group were markedly decreased (P<0.01), while expression of IL-4 mRNA was significantly increased (P<0.01). Expressions of IL-2 and interferon-γ mRNA in CD4⁺ T lymphocytes of rats in VNS group were obviously increased when compared with those of rats in sepsis group (P<0.01), while expression of IL-4 mRNA was markedly decreased (P<0.01). In comparison with those of rats in sepsis group, expressions of IL-2 and interferon-γ mRNA in CD4⁺ T lymphocytes of rats in VGX group were markedly decreased (P<0.01), while expression of IL-4 mRNA was significantly increased (P<0.01). Conclusions Electrical stimulation of vagus nerve can significantly improve multiple organ dysfunction and reverse immunosuppression of T lymphocytes in septic rats, while vagotomy of vagus nerve may enhance the susceptibility of rats to sepsis.