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Portulaca oleracea L. is a traditional oriental medicine known for its pharmacological effects. The present study aimed to investigate the immunostimulatory effects of PPCE on cyclophosphamide-stimulated rat model and in isolated spleen cells. The result showed that PPCE exerted an immunostimulatory effect in vivo and in vitro. Specifically, PPCE significantly enhanced splenocyte proliferation and upregulated inflammatory cytokines (IL-2, IL-12, TNF-α, and IFN-γ) and NK cell activity in vitro. The immunostimulatory effect was further investigated through various immunological assays. Oral administration of PPCE increased the swimming time and number of immune cells in rats. Histological analysis revealed that PPCE administration exerted splenic recovery. Thus, P. oleracea L. based complex extracts may be used as an immunostimulatory agent in medicine or functional foods. [ABSTRACT FROM AUTHOR]