Brown algae (BA) have recently gained high interest as a beneficial source of pharmacological numerous invaluable active constituents. Subsequently, water-soluble polysaccharides of BA attracted the attention of researchers worldwide due to their anticancer and antioxidant activities. This study was carried out to evaluate the anti-inflammatory activity of polysaccharides (PLS) extract of Padina boergesenii brown algae. Xylene produced-ear inflammation and carrageenan produced-paw edema models were used in this study. The PLS doses of 75, 125, 250, 500, 750, 1000mg/kg were tested. Our obtained data revealed that PLS inhibited the inflammatory reactions of both models in a dose-dependent manner. Interestingly, the anti-inflammatory effect of PLS is associated with lowering of nitric oxide and MDA free radicals and pro-inflammatory cytokines: IL- 1β, IL-6, and TNF-α level. This data highlights the therapeutic significance of isolated PLS. As this polysaccharide possesses high anti-inflammatory activity in comparison to the anti-inflammatory drug diclofenac, therefore this natural compound could be recommended as a new effective remedy for inflammation.