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The intestinal mucosal barrier plays an important role in systemic immune functions. This study aimed to find the mechanism of peptide from Alaska Pollock (APP) on intestinal mucosal immunity in mice induced by cyclophosphamide (Cy). Cy-induced decreases of body weight and index of immune organ were significantly improved by APP as compared with Cy group (p < 0.05). APP could promote the secretion of SIgA and IgA on intestinal mucosa (p < 0.05) and mainly had an impact on the final differentiation of IgA+ B cell, thereby promoting the secretion of plasma cells, which can be corroborated by the increases of IL-6 and IL-10 (p < 0.05). APP with high immune activity was separated and two peptides were purified and identified as Gly–Val–Ile–Lys and Ala–Cys–Asn–Gly–Arg. Therefore, APP can be considered as beneficial ingredients to protect the intestinal barrier disruption induced by Cy.

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