Although exercise has been recommended for the treatment of hypertension (HTN), the precise mechanisms of effects of exercise training (ExT) in HTN remain largely unexplored. Based on our recent unpublished results, here we tested the hypothesis that central increase in GSK-3β activity would cause reversal of effects of ExT in HTN. To increase GSK-3β activity in the brain, we chronically injected Triciribine (TCN) by intracerebroventricular (ICV) route. 90 Sprague-Dawley rats were randomized into six groups (n=15/group): 1) Sal+Ex+Veh; 2) Sal+Ex+TCN; 3) AngII+Sed+Veh; 4) AngII+Sed+TCN; 5) AngII+Ex+Veh; 6) AngII+Ex+TCN (Sal, saline; Ex, exercise; Veh, vehicle; Sed, sedentary). Rats were given AngII (hypertensive) or Veh (Normotensive) via osmotic minipumps. Groups 1, 2, 5, and 6 received moderate-intensity ExT for 42 days; groups 3 and 4 were sedentary. MAP was measured by radio-telemetry and cardiac function by echocardiography. The PVN tissues were examined for TNF, IL-1β, IL-10, and oxidative stress markers (iNOS, NOX2) levels. ExT delayed the progression of HTN, and improved cardiac hypertrophy and function in hypertensive rats. Chronic ICV infusion of TCN prevented these beneficial changes (Table). TCN prevented exercise-induced improvement in balance between pro- and anti-inflamamtory cytokines as well as exercise-induced reduction in oxidative stress within the PVN of hypertensive rats. These findings provide direct evidence that the beneficial effects of regular moderate-intensity ExT in HTN are mediated, at least in part, by reduced activation of central GSK-3β and potentially via improvement in inflammatory cytokines and oxidative stress within the PVN.