Abstract Objective To investigate the effect of fructose consumption on the light/dark pattern of blood pressure, heart rate and autonomic neural function in mice. Background Insulin resistant diabetes is associated with hypertension and autonomic dysfunction. There is evidence that the increasing incidence of diabetes may be related to dietary changes, including consumption of high levels of fructose. Design/methods C57/BL mice, instrumented with radiotelemetric arterial catheters, were fed a control or high fructose diet (60%). Cardiovascular parameters measured were light/dark pattern of mean arterial pressure (MAP), heart rate (HR) and variability (time and frequency domain). We also measured plasma insulin, glucose, lipids and angiotensin II (Ang II) as well as glucose tolerance. In situ hybridization was used to measure brainstem expression of tyrosine hydroxylase (TH) and Ang AT1a mRNA. Results Fructose diet (8 weeks) produced an increase in MAP, variance and low frequency domain (14 ± 3 vs. 33 ± 4 mm Hg 2, variance and 10 ± 2 vs. 26 ± 4 mm Hg 2, LF, control vs. fructose, P < 0.01). The changes occurred only at night, a period of activity for mice. Glucose tolerance was attenuated in the fructose group. Fructose also increased plasma cholesterol (80 ± 1 vs. 126 ± 2 mg/dl, control vs. fructose, P < 0.05) and plasma Ang II (18 ± 5 vs.65 ± 12 pg/ml, control vs. fructose, P < 0.05). Depressor responses to α 1-adrenergic blockade with prasozin were augmented in fructose-fed mice. Using quantitative in situ hybridization, we found that Ang AT1a receptor and TH mRNA expression were significantly increased in the brainstem locus coeruleus. Conclusion A high fructose diet in mice produced nocturnal hypertension and autonomic imbalance which may be related to activation of sympathetic and angiotensin systems.