In the present study, we investigated whether lentinan, a dietary β-1,3;1,6-glucan derived from Lentinula edodes, exerts anti-inflammatory activities using an in vivo and an in vitro model of gut inflammation, and we provide evidences that lentinan inhibits gut inflammation through modulation of TNFR1 expression in IECs. This evidence concerns the gene TNFRSF1A and inflammation.