Background This study was undertaken to investigate whether coronary flow reserve (CFR) using coronary sinus flow (CSF), which can be measured by transesophageal Doppler echocardiography (TEDE), especially when contrast enhanced, is useful in evaluating microvascular dysfunction in patients with diabetes mellitus (DM). Methods and Results CSF recordings using contrast enhanced TEDE were performed before and after adenosine triphosphate infusion (0.15 mg · kg^-1 · min^-1) in 16 patients with type 2 DM and diabetic retinopathy and in 13 non-DM patients (control). Coronary angiography revealed normal epicardial coronary arteries. CFR was defined as the ratio of the antegrade flow velocity time integral in hyperemic conditions and basal levels. Clear envelopes of CSF were obtained in all DM patients using contrast-enhanced TEDE. CFR using CSF in the DM group was significantly decreased compared with the control group (1.4±0.4 vs 2.1±0.5, p<0.01), but there were no significant differences of age, ejection fraction, rate of hypertension and hypercholesterolemia between the 2 groups. Using 1.7 of CFR as the cut-off value, diabetic microvascular dysfunction could be detected with 82% sensitivity and 83% specificity. Conclusions CFR calculated by CSF using contrast-enhanced TEDE may be useful for evaluating diabetic microvascular dysfunction. (Circ J 2006; 70: 1415 - 1420)