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Cyclophosphamide (CTX) was used to establish the immunosuppressive mice model. The immune organ viscera index, phagocytes vitality, the levels of cytokines in serum, the oxidative stress resistance, proteomics and intestinal flora in mice were investigated to evaluate the effect of immune regulation of Nigella sativa seed polysaccharide (NSSP). The results showed that the high-dose NSSP group could significantly increase the thymus and spleen index. The levels of ACP, LDH, T-AOC, SOD, IL-2, IL-4 and IL-6 were significantly increased an