Fucoidan has been reported to present diverse bioactivities, but each extract has specific features from which a particular biological activity, such as immunomodulation, must be confirmed. In this study a commercially available pharmaceutical-grade fucoidan extracted fromFucus vesiculosus, FE, was characterized and its anti-inflammatory potential was investigated. Fucose was the main monosaccharide (90 mol%) present in the studied FE, followed by uronic acids, galactose, and xylose that were present at similar values (3.8–2.4 mol%). FE showed a molecular weight of 70 kDa and a sulfate content of around 10%. The expression of cytokines by mouse bone-marrow-derived macrophages (BMDMs) revealed that the addition of FE upregulated the expression of CD206 and IL-10 by about 28 and 22 fold, respectively, in respect to control. This was corroborated in a stimulated pro-inflammatory situation, with the higher expression (60 fold) of iNOS being almost completely reversed by the addition of FE. FE was also capable of reverse LPS-caused inflammation in an in vivo mouse model, including by reducing macrophage activation by LPS from 41% of positive CD11C to 9% upon fucoidan injection. Taken together, the potential of FE as an anti-inflammatory agent was validated, both in vitro and in vivo.