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Objective: This study investigated the effect of catheter-based renal sympathetic denervation (RDN) in pigs with rapid pacing induced heart failure., Methods: Heart failure was induced by rapid right ventricular pacing in 12 pigs and pigs were randomly divided into RDN group (n = 6): pacing+RDN at 7 days post pacing; control group (n = 6): pacing only. Echocardiography examination (LVEF, LVEDD and LVESD) was performed before pacing and at 1 and 2 weeks post pacing. Serum biochemical markers including renin, aldosterone and creatinine were also measured at baseline, 1 and 2 weeks after pacing. Repeated renal artery angiography was performed at 1 week after RDN. All pigs were sacrificed to examine the heart and renal pathology and renal artery sympathetic nerve staining at 2 weeks post pacing., Results: LVEF decreased 1 week after rapid pacing from (60.5 ± 6.0)% to (35.3 ± 9.8)%. LVEF was significantly higher [(42.8 ± 5.9) % vs. (33.4 ± 9.7)%, P = 0.001 8] while LVESD was significantly lower [(28.4 ± 3.7) mm vs. (33.0 ± 2.0) mm, P = 0.001 6] in the RDN group than in the control group at 2 weeks post pacing. At 2 weeks after pacing, plasma concentrations of renin and aldosterone were significantly lower in RDN group compared to the control group (all P < 0.05) . Kidney function and blood pressure were comparable between the two groups at 2 weeks post pacing. There were no signs of renal damages such as renal artery stenosis, dissection and thrombus in all pigs after 2 weeks pacing. Sympathetic neurons of adventitia were injured in RND group., Conclusion: RDN could significantly improve cardiac function and attenuate left ventricular remodeling via inhibiting renin-angiotensin-aldosterone system in this pacing induced pig heart failure model.