This article deals with the nutritional aspect of fresh water mussel Lamellidens marginalis and its pharmacological potential in inflammatory disorders. Fresh water mussel extract shows anti-inflammatory activity after oral supplementation. Therefore, the present work was aimed to elucidate anti-inflammatory activity of Lamellidens lipid in in vivo adjuvant induced arthritis and in vitro LPS induced macrophage activation model, where its activity was compared with pharmaceutical grade EPA-DHA supplement. Parameters that showed better response to mussel lipid, than to EPA-DHA supplement, were paw and ankle diameters, paw weight, urinary hydroxyproline, glucosamine, serum phosphatases, macrophage lipid peroxidation level and pro-inflammatory interleukin level in adjuvant induced arthritis and TNFα, NO level, intracellular ROS generation as well as nuclear translocation of NFκB p65 in LPS activated in vitro primary macrophage culture. Fresh water mussel lipid was found to have lower n3:n6 ratio than that in marine species but contain all the major n3 fatty acids. This study, for the first time, showed anti-inflammatory potential of lipid from a fresh water species. It has also raised the possibility of the presence of balanced fatty acid combination in a dietary dose, rather than the established EPA-DHA supplement, to be more effective against inflammatory conditions of arthritis and LPS stimulated macrophages. © 2015 Elsevier B.V..