This study was conducted to further explore the effects of selenium on the blood antioxidant capacity in rats exposed to fluoride to find out the optimal dosage level of selenium. Animals were divided into prevention sequence (Selenium???NaF, water???NaF) and treatment sequence (NaF???Selenium, NaF???water) (sodium fluoride 50 mg/L; sodium selenite 0.375, 0.75, 1.5 mg/L). The exposure time was 12 months. Then, the fluidity of erythrocyte membrane by electron spin resonance was analyzed, and the blood was collected for GSH-Px and SOD activity, total antioxidant capacity (T-AOC) and uric acid assay, sialic acid and MDA content. The results showed that, compared with control group, GSH-Px activity and T-AOC level increased significantly (P?<?0.05), and SOD activity was raised in varying degrees in prevention and treatment groups, respectively. Uric acid level was up-regulated, but no significant differences were observed (P?>?0.05). The fluidity of erythrocyte membrane showed significant increase (P?<?0.05). As evident in this study, when the dose of selenium was 0.75 mg/L, all the activities of antioxidant enzymes increased significantly in prevention sequence; but in treatment sequence, the optimum intervention concentration was 1.5 mg/L. On the basis of results, the preventive effect of selenium was superior to treatment effect on the oxidative stress induced by an overdose of fluoride.