This study tested whether leptin restores sympathetic-vagal balance, heart rate (HR) variability and cardiac baroreflex sensitivity (BRS) in streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were instrumented with arterial and venous catheters and a cannula was placed in the lateral ventricle for intracerebroventricular (ICV) leptin infusion. Blood pressure (BP) and heart rate (HR) were monitored by telemetry. BRS and HR variability were estimated by linear regression between HR and BP responses to phenylephrine or sodium nitroprusside and autoregressive spectral analysis. Measurements were made during control period, 7 days after induction of diabetes, and 7 days of ICV leptin infusion. STZ-diabetes was associated with hyperglycemia (422±17 mg/dl) and bradycardia (-79±4 bpm). Leptin decreased glucose levels (165±16 mg/dl) and raised HR to control values (303±10 to 389±10 bpm). Intrinsic HR (IHR) and chronotropic responses to full-blocking dose of propranolol and atropine were reduced during diabetes (260±7 vs 316±6, -19±2 vs -43±6 and 39±3 vs 68±8 bpm) and leptin treatment restored these variables to normal (300±7, -68±10 and 71±8 bpm). Leptin normalized BRS (bradycardia: -2.6±0.3, -1.7±0.2 and -3.0±0.5; tachycardia: -3.2±0.4, -1.9±0.3 and -3.4±0.3 bpm/mmHg for control, diabetes and leptin) and HR variability (23±4 to 11±1.5 ms²). Chronic glucose infusion to maintain hyperglycemia during leptin infusion did not alter leptin's effect on IHR but abolished the improved BRS. These results show rapid impairment of autonomic nervous system control of heart rate after induction of diabetes and that leptin's CNS actions can abolish the hyperglycemia as well as the altered IHR and BRS in STZ-induced diabetes.