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Diabetes increases the risk for cerebromicrovascular disease, possibly through its effects on blood flow regulation. The aim of this study was to assess the effects of type 2 diabetes on blood flow velocities (BFVs) in the middle cerebral arteries and to determine the relationship between white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) and BFVs.We measured BFVs in 28 type 2 diabetic and 22 control subjects (aged 62.3 ± 7.2 years) using transcranial Doppler ultrasound during baseline, hyperventilation, and CO2 rebreathing. WMHs were graded, and their volume was quantified from fluid-attenuated inversion recovery images on a 3.0 Tesla MRI.The diabetic group demonstrated decreased mean BFVs and increased cerebrovascular resistance during baseline, hypo- and hypercapnia (P < 0.0001), and impaired CO2 reactivity (P = 0.05). WMH volume was negatively correlated with baseline BFV (P < 0.0001). A regression model revealed that baseline BFVs were negatively associated with periventricular WMHs, HbA1c (A1C), and inflammatory markers and positively associated with systolic blood pressure (R2 = 0.86, P < 0.0001).Microvascular disease in type 2 diabetes, which manifests as white matter abnormalities on MRI, is associated with reduced cerebral BFVs, increased resistance in middle cerebral arteries, and inflammation. These findings are clinically relevant as a potential mechanism for cerebrovascular disease in elderly with type 2 diabetes.