The anti-inflammatory (AI) activity of a supercritical fluid extract (CO(2)-SFE) of tartaric acid-stabilised Perna canaliculus mussel powder, and of the free fatty acid (FFA) class separated from the CO(2)-SFE extract by column chromatography, was investigated in the rat adjuvant arthritis model. Administration of the CO(2)-SFE extract (100 mg/kg BW/day s.c.) for 15 days post-adjuvant inoculation significantly reduced rear paw swelling by 34% and the deterioration in total body condition by 52% in arthritic rats, compared to vehicle controls. These observations were accompanied by a decreased serum ceruloplasmin oxidase activity, and reduced inflammatory response of the spleen. The mussel FFA extract given at one third of the dose (30 mg/kg BW/day s.c.) and for a shorter treatment period (5 days during the inflammatory phase) achieved an even greater AI activity, and was equipotent to piroxicam (2 mg/kg BW/day s.c.). Preliminary toxicology assessment using both arthritic and non-arthritic (healthy) rats revealed no significant differences between the mussel treatment groups and respective vehicle controls in either organ weights, tissue histology or selected biochemical parameters. These results indicate the CO(2)-SFE crude lipid extract and its FFA components from stabilised P. canaliculus mussel powder contain biologically significant AI activity in vivo, with no apparent adverse side effects.