The effect of glucosamine and vitamin E against rheumatoid arthritis (RA) in a neonatal rat model was investigated. Lipid peroxidation, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), glutathione peroxidase (Gpx), matrix metalloproteinase-3 (MMP-3), prostaglandin E2 (PGE2), ceruloplasmin, copper, zinc, nitric oxide (NO), uric acid, inducible nitric oxide synthase (iNOS), and nuclear factor-kappaB (NF-κB) levels were determined in control and rheumatoid arthritis neonatal rats. Glucosamine plus vitamin E supplementation reduced the MDA level by 61.9% and increased the SOD, catalase, GSH, Gpx, and zinc levels. MMP-3, PGE2, ceruloplasmin, copper, NO and uric acid levels were significantly reduced by supplementation of glucosamine plus vitamin E. NF-κB, and iNOS protein levels were decreased by 47.7% and 39.5%, respectively, by glucosamine plus vitamin E supplementation. Thus, supplementation with glucosamine plus vitamin E exerted a synergistic effect against RA.