The present study investigates the immunomodulatory activities of buckwheat polysaccharide fraction (BPF) from the seed of Fagopyrum esculentum on RAW 264.7 macrophage cell line and Cyclophosphamide-induced immunosuppressed conditions in mice models. The results of in vitro showed that treatment with 0.5-10 mu g/mL of BPF can modulate immune responses. MIT assay and nitric oxide production and immune-related cytokine levels were conducted. Treatment with BPF at a dose of 10 mu g/mL of BPF increased immune responses on macrophages. Moreover, natural killer (NK) cell cytotoxicity was conducted. The apoptosis of YAC-1 cells increased as the co-culture ratio between spleen cells and YAC-1 cells increased approximately 4- fold compared to the control group from 12.5:1 to 50.0:1. The in-vivo immunomodulatory effects of BPF were evaluated by cyclophosphamide-induced mice model. The immune response of BPF was determined against cyclophosphamide (100 mg/kg) immunosuppressed mice at doses of 50 mg/kg and 100 mg/kg of BPF as compared to control. The results of this study showed that BPF administration increased spleen and thymus indices as well as the leukocytes count in the blood of immunosuppressed mice. All of results suggested that BPF are potentially acts as immunomodulator for activation of immune responses. (C) 2018 Elsevier Inc. All rights reserved.