A naturally occurring fatty acid, conjugated linoleic acid (CLA), reduces immune-induced TNF and inducible cyclooxygenase (COX-2) expression; key mediators of inflammation in rheumatoid arthritis (RA). Based on previous work, it was hypothesized that dietary CLA would act as an anti-inflammatory agent in select animal models of RA. In the collagen antibody-induced arthritis (CAIA) model, mice fed CLA (c9, t11 and t10, c12-CLA) for 3 weeks before anti-collagen antibody injection had reduced lipopolysaccharide-induced plasma TNF levels and had arthritic scores that were 60% of mice fed corn oil (CO). In the collagen-induced arthritis (CIA) model, mice fed CLA for 21 days prior to immunization had lower IgG₁ titers, earlier signs of joint inflammation, but similar arthritis scores when compared to CO fed mice during the remaining 70 day post injection period. Beginning on day 80 to 133, CLA fed mice had arthritic scores 70% that of the CO fed mice. In a second CIA experiment, CLA was fed only after the booster injection. Plasma IgG₁ levels were not reduced and arthritis onset was delayed 4 days in CLA fed mice as compared to the CO fed mice. Peak arthritis score was similar between CLA and CO fed mice from day 35 to 56. Since CLA reduced inflammation in the CAIA model, delayed onset of arthritis in the CIA model (CIA experiment 2) and reduced arthritis score after day 80 in the CIA model (CIA experiment 1), we concluded that dietary CLA exhibited anti-inflammatory activity that was dependant on antibody.