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Polysaccharide Of Atractylodes Macrocephala Koidz (PAMK) has been proved to have anti-cancer, antitumor, anti-inflammation function and improve the immune level of the organism. The miRNA plays a very important role in regulating the immune function by negatively regulate the expression of target genes. To explore the molecular mechanism of PAMK active the lymphocytes, thirty 61-d-old geese were randomly divided into 4 groups (C, CTX, PAMK, PAMK+CTX). The thymus morphology, the level of serum granulocyte-macrophage colony-stimulating factor (GMC-SF), IL-1β, IL-3, IL-5, the relative mRNA expression of CD25, novel_mir2, CTLA4 and CD28 signal pathway were measured. Further more, the lymphocytes was extracted from thymus to measure the relative mRNA expression of CD28 signal pathway. The results showed that PAMK could significantly maintain normal cell morphology of thymus, alleviate the decrease level of GMC-SF, IL-1β, IL-5, IL-6, TGF-β, the increase level of IL-4, IL-10, and the decrease relative mRNA expression of novel_mir2, CD25 and CD28 signal pathway in thymus and lymphocytes induced by cyclophosphamide (CTX). In conclusion, PAMK alleviated the decreased T lymphocytes activation levels induced by CTX through novel_mir2/CTLA4/CD28/AP-1 signal pathway. [ABSTRACT FROM AUTHOR]