There are many active substances in Atlantic cod (Gadus morhua) explaining the variety of biological activities. In order to study the immunomodulatory activity and the mechanism of Atlantic cod peptides at the cellular level. In this study, cod peptides were isolated by 80% ethanol extraction method, the isolated ethanol-soluble cod peptides (CP-ES) were investigated and their immunomodulatory activity was verifi ed. Additionally, CP-ES showed lower molecular weight and more hydrophobic amino acids. CP-ES could promote the proliferation of spleen lymphocytes and T lymphocytes in mice, suggesting that CP-ES may regulate adaptive immunity. It promoted the release of NO and the expression of iNOS, TNF-α, IL-6 and IL-1β genes in macrophages, suggesting that CP-ES may regulate innate immunity. CP-ES could promote the expression of TLR2 gene, and the peptides identifi ed in CP-ES were docked with TLR2 to predict the peptides playing a major role in CP-ES. These results suggested that CP-ES may regulate the immune activity of both innate and adaptive lines.