Purpose: To evaluate the additional diagnostic value of a specific quantification methodology applied to routine MPS in the evaluation of coronary blood flow reserve in a group of patients with type-2 DM. Materials and Methods: We applied single-day rest-stress MPS to 38 diabetic patients over 50 years of age, with DM durations longer than 10 years, and without hypertension, cigarette smoking, known coronary artery disease, or previous myocardial infarction; and to an age-matched control group of 19 patients with low risk for coronary artery disease. Using left ventricular myocardial counts obtained from SPECT data and the injected amounts of Tc-99m sestamibi, we calculated the relative increase in myocardial counts during exercise in comparison to rest conditions, as % IR, for each patient. Results: The calculated % IR values were lower in diabetic patients, although the difference was not statistically significant (p = 0.27). Because MPS revealed myocardial ischemia in 5 diabetic and 2 control patients, statistical analysis was repeated after exclusion of these ischemic patients. However, the result of this analysis was similar (p = 0.27). In the whole study groups, % IR values were significantly lower in patients with myocardial ischemia compared to patients with normal MPS findings (p = 0.02). Conclusion: With respect to % IR values, no significant difference was found between diabetic patients and the control group. However, the finding that % IR values were lower both in diabetics compared to controls and in ischemic patients compared to non-ischemic patients is promising for the applicability of quantitative analysis of routine MPS data and its possible contribution to the diagnosis of coronary artery disease.