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The results demonstrated that COP1 ameliorated the body weight and immune organ (spleen and thymus) index of mice and improved the pathological changes of the spleen and ileum induced by CY. COP1 strongly stimulated the production of inflammatory cytokines (IL-10, IL-12, IL-17, IL-1\u03b2, and TNF-\u03b1) of the spleen and ileum by promoting the mRNA expressions. Furthermore, COP1 had immunomodulatory activity by increasing several transcription factors (JNK, ERK, and P38) in the mitogen-activated protein kinase (MAPK) signaling pathway. Related to the above immune stimulatory effects, COP1 positively affected the production of short-chain fatty acids (SCFAs) and the expression of ileum tight junction (TJ) protein (ZO-1, Occludin-1, and Claudin-1), upregulated the level of secretory immunoglobulin A (SIgA) in the ileum and microbiota diversity and composition, and improved intestinal barrier function. 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