Oligosaccharides that mimic heparan sulfate (HS) exhibit a variety of biological activities. One such oligosaccharide, λ-CO, a λ-carrageenan-derivative previously shown to inhibit cell migration, invasion, and heparanase 1 (HPA1), was evaluated for its anti-inflammatory properties. In LPS-stimulated macrophages, λ-CO significantly reduced Il-6 and Tnf-α production, as well as Erk and Akt phosphorylation, and Mmp-2/Mmp-9 secretion, independently of Hpa1 activity. In primary human keratinocytes stimulated with the psoriasis-mimicking M5 cytokine cocktail, λ-CO down-regulated cathepsin L and MMP-9 expression, as well as several M5-induced inflammatory genes. In vivo , λ-CO (1 and 10 mg.kg⁻¹) was administered in the imiquimod-induced mouse model of psoriasiform inflammation. Although no overt macroscopic improvement in skin lesions was evident, λ-CO at 10 mg.kg⁻¹ downregulated several inflammation-related genes in the skin and significantly reduced serum Mmp-9 levels. Taken together, these results suggest that λ-CO is a potential anti-inflammatory agent that selectively inhibits MMP-9 expression. This supports its further development as an adjunct to biotherapies for inflammatory skin disorders such as psoriasis.