Exercise training (ExT) has been shown to be a safe and effective method to improve functional status and quality of life in chronic heart failure (CHF). Unfortunately, the cellular, molecular and neural mechanisms that account for these beneficial effects are largely unknown. Studies in our laboratory have shown that ExT in animals with CHF reduces both global and renal sympathetic nerve activity (RSNA). Coincident with the decrease in RSNA, we found a decrease in central angiotensin type 1 receptor expression and oxidative stress in the rostral ventrolateral medulla (RVLM). Furthermore, ExT evoked an increase in antioxidant enzyme production in the RVLM. Both CuZn SOD and Mn SOD were increased in CHF animals following ExT. NADPH oxidase was also increases in CHF and normalized following ExT. Transfection with CuZn SOD adenovirus mimics the beneficial effects of ExT in CHF animals. In studies designed to evaluate the role of ExT on renal blood flow (RBF) regulation, ExT was carried out in chronically instrumented rabbits with CHF. Following ExT rabbits were stressed with acute exercise and 5% hypoxia. Sedentary CHF rabbits exhibited profound decreases in RBF and conduction in response to acute stress. However, ExT CHF rabbits exhibited responses that were similar to normal rabbits. Infusion of the α1 adrenergic blocker prazosin only partially (about 50%) restored RBF responses in CHF sedentary rabbits suggesting that the normalization of stress responses in ExT CHF rabbits is due to factors in addition to a reduction in α1 receptor stimulation. In total, these studies strongly suggest that ExT in the setting of CHF mediates a reduction in sympatho-excitation by a central ROS mechanism and by an effect on peripheral sympathetic signaling.