The renin angiotensin system (RAS) has been implicated in the cardiovascular complications of diabetes. We showed that a high fructose diet increases blood pressure and plasma angiotensin (Ang) and impairs glucose tolerance. We investigated the role of Ang AT1a receptors in the development of fructose-induced cardiovascular and metabolic dysfunction. Male Ang AT1a knockout (AT1aKO) and wild type (AT1aWT) mice with arterial telemetric catheters were fed a standard diet or one containing 60% fructose. Fructose increased mean arterial pressure (MAP) in AT1aWT, but only during the dark phase (8% increase). In AT1aKO, fructose, unexpectedly, decreased MAP, during both light and dark periods (24% and 13% decrease, respectively). Analytical methods were used to measure systolic arterial pressure (SAP) and pulse interval (PI) variability in time and frequency domains. In fructose-fed AT1aWT there was an increase in SAP variance and its low frequency domain (11±3 vs. 23±4 mmHg², variance and 7±2 vs. 17±3 mmHg², LF, control vs. fructose, p< 0.004). There were no changes in SAP variance in AT1aKO. Depressor responses to ₁- adrenergic blockade were augmented in fructose-fed AT1a WT as compared to AT1aKO. Fructose inhibited glucose tolerance with a greater effect in AT1aWT. Fructose increased plasma cholesterol in both groups (p <0.01) and reduced Ang II in AT1aKO. Results document prominent interactions between genetics and diet with data showing that in the absence of Ang AT1a receptors, a fructose diet decreased blood pressure.