Objective To investigate effect of Dendrobium huoshanense on immune function in a rat model of chronic atrophic gastritis with spleen-Yin deficiency. Methods A total of 36 Sprague-Dawleyrats were randomly divided into normal group, model group, and low-, middle-, and high-dose Dendrobium huoshanense groups, with 6 rats in each group, and a rat model of chronic atrophy gastritis with spleen-Yin deficiency was established by the administration of N-methyl-N′-nitro-N-nitrosoguanidine combined with Yin-deficiency drugs (Radix Aconiti Lateralis Preparata, dried ginger, and cinnamon) and the fatigue method.The low-, middle-, and high-dose Dendrobium huoshanense groups were given aqueous suspension of Dendrobium huoshanense(0.7, 1.4, and 2.8 g/kg, respectively) by gavage for 21 days, and the normal group and model group were given an equal volume of normal saline by gavage for 21 days.After successful modeling,Dendrobium huoshanense was given by gavage for 21 consecutive days, and the rats in each group were observed in terms of activity, body weight, spleen index and thymus index, spleen histomorphological changes, peripheral blood T lymphocyte subsets, and leukocyte count and classification. ELISA was used to measure the serum levels of immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG), as well as the levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10) in serum and gastric mucosa. Results All treatment groups had significant increases in spleen index and thymus index, an improvement in the histopathological status of the spleen, and significant increases in the levels of immunoglobulins (IgA, IgM, and IgG) in serum, as well as varying degrees of increases in the levels of cytokines IL-2 and TNF-γ and varying degrees of reductions in the levels of IL-4 and IL-10 in serum and gastric mucosa. In addition,Dendrobium huoshanense improved peripheral blood leukocyte count, absolute value of lymphocytes, and absolute neutrophil count, upregulated peripheral blood CD3+, CD4+, and CD4+/CD8+ ratio, and downregulated the percentage of CD8+ T lymphocytes. Conclusion Dendrobium huoshanense can improve immune function in a rat model of chronic atrophic gastritis with spleen-Yin deficiency.