To study the effects and immunomodulatory action of Shenqi Qiangjing Granules on rats with chronic fatigue syndrome(CFS) with spleen-kidney yang deficiency.Methods:A total of 50 specific pathogen-free(SPF) healthy male SD rats were randomly divided into normal control group，model control group as well as high，medium and low dose groups of Shenqi Qiangjing Granules.Physical fatigue of rats was caused by exhaustive swimming，psychological fatigue of rats by chronic restraint stress，and spleen-kidney yang deficiency by gavage of senna leaf decoction，thus establishing a CFS rat model of spleen-kidney yang deficiency.After the model was successfully established，the rats gavaged with the respective dosages of Shenqi Jiangjing Granules for 21 consecutive days.Thymus and spleen indexes were detected，serum immunoglobulin(IgG)，immunoglobulin M(IgM)，immunoglobulin A(IgA) concentrations，and cytokines interleukin-2(IL-2)，interleukin-6(IL-6)，and interferon-gamma(IFN-γ) were measured by enzyme-linked immunosorbent assay(ELISA).The proliferative abilities of splenic T and B lymphocytes in spleen were assessed by MTT method，and the distribution of peripheral blood T lymphocyte subpopulations was analyzed by flow cytometry.Results:The behavioral results showed that，the CFS model rats showed slow body weight gain，lethargy，reduced food and water intake，reduced activity，loose stools，reduced exhaustive swimming time，and increased tail suspension immobility time.After medication intervention，compared with the model group，the treatment groups showed significant improvements in mental state，body weight，as well as food and water intake，and increased exhaustive swimming time，and decreased tail suspension immobility time(P<0.01 or P<0.05); And each dose of Shenqi Qiangjing Granules can significantly increase the index of thymus and spleen in rats，and could improve the concentration of IgG，IgM，IgA and content of IL-2，IL-6，IFN-γ; In addition，Shenqi Qiangjing Granules can significantly improve the proliferation of splenic T and B lymphocytes in the spleen，and it can also increase the percentage of CD3+，CD4+T lymphocytes and the ratio of CD4+/CD8+T，while reducing the percentage of CD8+T lymphocytes，with significant differences(P<0.01 or P<0.05).Conclusion:Shenqi Qiangjing Granules can significantly improve the immune function and and relieve fatigue symptoms in rats with CFS characterized by spleen-kidney yang deficiency，demonstrating a good immunomodulatory effect.