Background: SGLT2 inhibitors may have protective effects on cardiac and renal injuries; however, their mechanisms remain unclear. Sympathetic activation has a crucial role in cardio/renal injuries. This study aimed to investigate whether empagliflozin can inhibit cardio/renal injuries through sympathoinhibition in a rat model of hypertensive heart failure. Methods: Male Dahl salt-sensitive rats were divided into low-salt (LS) and high-salt (HS) diet groups from 6 weeks of age. The rats in HS group were assigned to vehicle (HS-VEH) or empagliflozin (HS-EMPA) treatment group at 8 weeks. The effect of empagliflozin on central sympathetic regulation and cardio/renal injuries was assessed at 12 weeks (pre-heart failure phase), while its protective effect on heart failure was evaluated at 15 weeks in another cohort. Results: At 12 weeks , systolic blood pressure was similarly elevated in HS-VEH and HS-EMPA. Plasma norepinephrine levels were increased in HS-VEH compared to LS, and were suppressed in HS-EMPA, which was consistent with the neuronal activity of pre-sympathetic neurons in the brain. Increased left ventricular (LV) weight/body weight, plasma creatinine levels, renal fibrosis, and glomerular sclerosis in HS-VEH were attenuated in HS-EMPA. At 15 weeks , the high salt-induced blood pressure elevation was similar between HS-VEH and HS-EMPA. Although LV hypertrophy did not significantly differ, both decreased echocardiographic LV fractional shortening and increased lung weight observed in HS-VEH were attenuated in HS-EMPA. Elevated plasma creatinine and norepinephrine levels in HS-VEH were also attenuated in HS-EMPA. Conclusion: Empagliflozin inhibits sympathoexcitation and ameliorates cardio/renal injuries without lowering blood pressure in the hypertensive heart failure model. This sympathoinhibitory effect of empagliflozin observed in the pre-heart failure phase might contribute to the attenuation of heart failure progression.