Controlled ozone administration has been shown to promote an oxidative preconditioning or adaptation to oxidative stress by increasing endogenous antioxidant systems. In the present study, the effects of ozone administration either prophylactically or therapeutically on the alterations of oxidant status in adjuvant arthritic rats have been studied. Seven groups of rats were used: (1) normal control group; (2) control arthritic group (21 days); (3) prophylactic ozone group: arthritic rats received fifteen intra-rectal applications of ozone/oxygen mixture at 0.5, 0.7 and one mg/kg b.wt. in a 5-6 ml volume starting one day before adjuvant inoculation and continued as five applications/week over 21 days; (4) oxygen group: received oxygen as vehicle for ozone in a manner similar to group 3; (5) control arthritic group (24 days); (6) therapeutic-ozone group: arthritic rats received ten intra-rectal applications of ozone/oxygen mixture at 0.5, 0.7 and one mg/kg b. wt. in a 5-6 ml volume daily for ten days starting fourteen days after adjuvant inoculation; (7) oxygen-treated group: received oxygen as vehicle for ozone in a manner similar to group 6. The effect of ozone administration was assessed by measuring: blood glutathione (GSH), erythrocyte glutathione peroxidase (GPx) and catalase (CAT) activities, serum levels of protein thiols (PrSHs), malondialdehyde (MDA) and nitrite/nitrate (NOx), as well as serum ceruloplasmin activity (CP). Results of the present study showed that adjuvant induced arthritis in rats caused a significant reduction in blood GSH, serum PrSHs levels and erythrocyte antioxidant enzyme activities accompanied by a marked increase in serum levels of MDA, NOx and CP activity. Ozone administration either prophylactically or therapeutically succeeded to normalize blood GSH, serum PrSHs and MDA levels and restored erythrocyte antioxidant enzyme activities. However ozone did not significantly modify elevated serum x level but augmented the increased CP activity in arthritic rat serum. So it could be concluded that ozone oxidative preconditioning effectively improved the antioxidant/oxidant imbalance associated with adjuvant arthritis in rats.