Objective: To evaluate the immunomodulating effect of oyster peptide on immunosuppressed mice. Methods: ICR mice injected with cyclophosphamide (CTX) were adopted as the module group, with mice without treatment as the control group, and different dosages of oyster peptide (0.5 g/kg, 1.0 g/kg, and 2.0 g/kg) were given to the low, middle, and high groups for 15 days. The body weight, spleen, and thymus weight of the mice, structures under the microscope of the immune organs, numbers of white blood cells, ratios of T lymphocyte subsets, immune cytokines and numbers of nuclear cells, and DNA content in bone marrow were all assessed. Results: Compared with the control group, the structures of thymus and spleen of the mice in the CTX group appeared obscure and shrunk when observed under microscope, the number of their white blood cells declined (P=0.04), the proportion of their CD3+T cells in peripheral blood declined (P=0.003), the proportion of their CD8+T cells in peripheral blood declined (P=0.002), the concentration of their IL-5 in peripheral blood significantly increased (P<0.01), the concentration of their nucleated cells and DNA density in bone marrow decreased (P=0.04, P<0.01). Oyster could improve the structures of thymus and spleen of the immunosuppressed mice. Compared with the CTX group, the number of white blood cells in 2.0 g/kg group increased (P=0.003), the proportion of CD3+T cells in peripheral blood in 1.0 g/kg group (P=0.04) and 2.0 g/kg group (P=0.02) increased, the proportion of CD8+T cells in peripheral blood in 2.0 g/kg group increased (P=0.002), the concentration of IL-5 in peripheral blood in all the oyster treated groups increased (P<0.01 in 0.5 g/kg, 1.0 g/kg, and 2.0 g/kg groups), the concentration of IL-17 in peripheral blood in 2.0 g/kg group decreased (P=0.03), the concentration of nucleated cells in bone marrow of all the oyster treated groups increased (0.5 g/kg vs. CTX, P=0.04; 1.0 g/kg vs. CTX, P=0.02; 2.0 g/kg vs. CTX P=0.01), the DNA content in bone marrow of all the oyster treated groups increased (P<0.01 in the 0.5 g/kg, 1.0 g/kg, and 2.0 g/kg groups). Conclusion: Oyster peptide could improve the structures of immune organs of the CTX-induced immunosuppressed mice, recover the imbalances of T lymphocyte subsets, improve the immune cytokines and increase numbers of nucleated cells and DNA content in bone marrow, thus improving the immunologic function.