The prevalence of RA is estimated to be 0.5-1% worldwide.<h4>Methods</h4>This work investigated the therapeutic effects and underlying mechanisms of blue mussel (<i>Mytilus galloprovincialis</i>) oil (BMO) on RA in rats, using green-lipped mussel oil (GMO) and Antarctic krill oil (KO) as controls.<h4>Results</h4>The results suggested that BMO, GMO, and KO all alleviated paw swelling in rats and reduced serum levels of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and pro-inflammatory cytokines such as TNF-α and IL-17. Here, TNF is linked to rheumatoid arthritis.