Polysaccharopeptide (PSP) is well known for its immunoregulatory effects. In the present study, the effect of PSP on white blood cell (WBC) count, T lymphocyte subsets, B lymphocytes, Th1/Th2 balance and negative immune regulators was investigated using an immunosuppressed mouse model. The results demonstrated that the WBC count and the absolute number of CD3+CD4+ T cells, CD3+CD8+ T cells and CD3‑CD19+ B cells in the peripheral blood were increased in PSP‑treated groups as compared with the cyclophosphamide (Cy) group. In addition, PSP reduced interleukin (IL)‑4 and GATA binding protein 3 (GATA‑3) mRNA relative expression levels and elevated the ratios of IL‑2/IL‑4 and the transcription factors, T‑box‑containing protein/GATA‑3. The relative mRNA expression levels of the forkhead/winged‑helix transcription factor box protein 3 (Foxp3), programmed death‑1 (PD‑1) and IL‑10 were also downregulated by PSP. These observations indicate that the immunoregulatory effects of PSP are associated with restoration of WBC number, improving the absolute number of T lymphocyte subsets and B lymphocytes, inducing the Th1/Th2 response and downregulating the negative immune regulators, Foxp3, PD‑1 and IL‑10.