Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly by tail cuff plethysmography. Because there are potentially significant drawbacks associated with plethysmography, we determined whether blood pressure changes could be detected by long-term monitoring with telemetry in age-matched male Sprague-Dawley rats fed either a normal or high-fructose diet for 8 weeks. Fasting plasma glucose (171 ± 10 versus 120±10 mg/dL), plasma insulin (1.8±0.5 versus 0.7±0.1 μg/L), and plasma triglycerides (39±2 versus 30±2 mg/dL) were modestly but significantly elevated in fructose-fed animals. Using the hyperinsulinemic euglycemic clamp technique, the rate of glucose infusion necessary to maintain equivalent plasma glucose was significantly reduced in fructose-fed compared with control animals (22.9±3.6 versus 41.5±2.9 mg/kg per minute; P<0.05). However, mean arterial pressure (24-hour) did not change in the fructose-fed animals over the 8-week period (111±1 versus 114±2 mm Hg; week 0 versus 8), nor was it different from that in control animals (109±2 mm Hg). Conversely, systolic blood pressure measured by tail cuff plethysmography at the end of the 8-week period was significantly greater in fructose-fed versus control animals (162±5 versus 139±1 mm Hg; P<0.001). Together, these data demonstrate that long-term fructose feeding induces mild insulin resistance but does not elevate blood pressure. We propose that previous reports of fructose-induced hypertension reflect a heightened stress response by fructose-fed rats associated with restraint and tail cuff inflation. © 2005 American Heart Association, Inc.