Aims: The aims of this study were to compare the index of microcirculatory resistance (IMR) and its determinants in diabetes mellitus (DM) and non-DM patients with vascular risk factors, and to evaluate the potential differential involvement of coronary microvascular beds. Methods and results: Fifty-six patients (32 with DM), without significant epicardial coronary disease, had IMR measured in the anterior and posterior circulations. There was no significant difference in the anterior compared to posterior circulation IMR in the whole group (27 vs. 26, p=0.92) or in the DM subgroup (35 vs. 28, p=0.31). DM patients had higher anterior circulation IMR compared to non-DM patients (27 vs. 15, p=0.009). Posterior circulation IMR was higher than anterior circulation IMR in non-DM patients (25 vs. 16, p=0.01). Multivariate determinants of higher anterior circulation DAR in DM were dyslipidaemia, hypertension, worsening glycaemic control, and higher body mass index; metformin had a protective effect. Conclusions: There is differential involvement of the coronary microvascular beds. In the presence of risk factors, microvascular function of the posterior circulation was affected before the anterior; DM patients had worse microvascular function in the anterior but not posterior circulation compared to patients without DM. Vascular risk factors, including DM, adversely affect coronary microvascular function, and their treatment was associated with improvement.