In the patients and animals with metabolic syndrome (MetS), sympathetic nerve activity (SNA) is increased. We have demonstrated that oxidative stress in the rostral ventrolateral medulla (RVLM), a vasomotor center in the brainstem, increases SNA. The aim of the present study was to determine whether calorie restriction inhibits SNA via anti-oxidant effect in the RVLM of obesity-induced obesity rats. Male Sprague-Dawley rats were fed on a high-fat diet and segregated into obesity-prone (OP) showing a MetS profile and obesity-resistant (OR) after 13 weeks. Obesity-prone was divided into OP treated with calorie restriction (CR-OP) for 8 weeks and control (CTR-OP). Systolic blood pressure (SBP), heart rate (HR), SNA, and thiobarbituric acid-reactive substances (TBARS) levels as a marker of oxidative stress in the RVLM were significantly higher and the depressor effects due to the microinjection of tempol, a superoxide dismutase mimetic into the RVLM, were significantly greater in OP than in OR. Body weight was significantly lower in CR-OP than in CTR-OP. SBP, HR, SNA, TBARS, and the depressor effects due to the microinjection of tempol into the RVLM were significantly lower in CR-OP than in CTR-OP. These results suggest that calorie restriction inhibits SNA via anti-oxidant effect in the RVLM of obesity-induced obesity rats.