Abstract Background: Elevated free radical generation in inflamed joints and impaired antioxidant system have been implicated in rheumatoid arthritis (RA). It is suggested that exercise improves the symptoms of rheumatoid arthritis, although the mechanism is not well understood. The aim of this study was to investigate the effect of swimming on the glutathione antioxidant system and oxidative changes induced by rheumatoid arthritis in rats. Methods: 8-week-old female Wistar rats were distributed within three groups (10 in each): A normal control group (C), a rheumatoid arthritis control group (RA+C), and a rheumatoid arthritis swimming exercise group (RA+EX). Rats at nine weeks of age were induced for rheumatoid arthritis by injection of complete Freund's adjuvant (20mg/kg) into the tail of Wistar rats. The arthritis was assessed grossly by walking ability, skin redness, and swelling in the joints. The RA+EX rats were conditioned to swim for the 4-week period (~20-60 min/day), whereas the other two groups remained sedentary in their cages. 48 hours after the last exercise session, a venous sample was collected to determine metabolic parameters, including glutathione peroxidase, glutathione reductase and lipid peroxidation products (malondialdehyde). The variance analysis test and the Tukey post-hoc test were applied to analyze the data (P<0.05). Results: Rheumatoid arthritis significantly increased levels of malondialdehyde, and swimming training prevented this response (P<0.05). Glutathione peroxidase was significantly decreased in the RA+C group compared to the RA+EX and C groups (P<0.05). In addition, the severity of rheumatoid arthritis clinical signs with RA+EX group was significantly lower than RA+C group (P<0.05). Conclusion: Our findings suggest that swimming may be useful in preventing the negative changes in glutathione antioxidant system and oxidative stress parameters of rheumatoid arthritis in rats. Key words: : Antioxidants, Glutathione Peroxidase, Rat