Objective To determine the role of the nucleus tractus solitarii (NTS) superoxide in mediating the chronic heart failure (CHF)-induced reduction in baroreflex control of sympathetic activity. Methods CHF model was produced by coronary ligation in SD rats, and rats receiving sham operation (Sham) served as controls. Changes in renal sympathetic nerve activity (RSNA) and baroreflex sensitivity control of sympathetic activity were observed after microinjections of SOD mimic Tempol into the NTS in Sham and CHF rats. Results In anesthetized rats, the baseline level of sympathetic nerve activity was significantly higher in CHF group than in Sham group (P<0.05), whereas the baroreflex sensitivity control of sympathetic activity was lower in CHF group than in Sham group. Bilateral microinjection of Tempol (10 nmol in 50 nL) into the NTS had no effect on baseline RSNA and baroreflex sensitivity in the Sham group. In contrast, injection of Tempol notably reduced the baseline RSNA and increased baroreflex sensitivity in CHF group. Conclusion Superoxide in the NTS contributes to sympathetic overactivity and baroreflex impairment in rats with CHF, suggesting that increased oxidative stress in the NTS is responsible for cardiovascular dysfunctions in CHF.