Microvascular dysfunction is a pathological hallmark of diabetes, and is central to the etiology of diabetes-associated cardiac events (e.g. myocardial infarction). Herein, previous studies have highlighted the role of the vasoactive micro-RNA 92a (miR-92a) in small, as well as large animal models. In this study, we explore the effects of miR-92a on human cardiac microvascular endothelial cells (HCMEC) and its underlying molecular mechanism. We show that diabetic HCMEC upregulate miR-92a, and inhibition of miR-92a improves tube formation (angiogenesis) as well as proliferation and migration of HCMEC. Furthermore, inhibition of miR-92a ameliorates diabetic endothelial bed inflammation by reducing monocyte recruitment and restoring levels of anti-inflammatory Krüppel-like Factors, KLF2 and KLF4. Our preliminary results suggest an involvement of miR-92a in the ADAM10/Notch signaling pathway by direct targeting and downregulation of the metalloprotease ADAM10. Altogether, our data suggest an involvement of miR-92a in the pathogenesis of cardiac microvascular EC dysfunction in diabetes, and a potential therapeutic target for nucleic-acid therapy.