We report here the discovery of a polysaccharide, namely EUP1, with anti-inflammatory activity from the herb of Eucommia ulmoides Oliv. We separated three polysaccharide fractions from this herb based on acidity and screened them for their activity in modulating the phenotype of murine macrophages. Among them, EUP1 was the only fraction to exert such a function − it stimulated Raw 264.7 cells to express CD206 and a key anti-inflammatory cytokine interleukin-10. Having fully characterised EUP1 with a series of chromatographic and spectroscopic analyses, we evaluated its anti-inflammatory effects in both in vitro and in vivo inflammatory models. In the murine model of sepsis induced by lipopolysaccharide, administration of EUP1 effectively suppressed the expression of major inflammatory cytokines, alleviated lung injury and increased animal survival rate. In summary, EUP1, with a clearly elucidated chemical structure and solid anti-inflammatory activity, may become a valuable candidate for further development into an anti-septic therapeutic agent.