Retinal pericytes are enigmatic cells. The lack of a panpericyte marker and the diversity of possible origins suggest that there is not one pericyte population in a given organ. The important functions of pericytes related to the specific demands of the retina are the control of endothelial survival and growth, and the tightness of the blood retinal barrier. Pericyte loss is a common early phenomenon of all diabetic mammalians. An important molecular contribution to pericyte functionality comes from the angiopoietin-Tie system that is involved in the maturation of the developing vascular network as well as in its destabilization and angiogenesis. Hyperglycemia induces upregulation of angiopoietin-2 which inhibits the pericyte-recruiting function of Ang-1 suggesting a novel, active, mechanism in pericyte loss, rather than a passive intoxication by glycolytic intermediates. Post-translational modification involving intracellular methylglyoxal-type AGEs and enzymatic modification of transcription factors are involved in glucose-induced transcription changes of Ang-2. Metabolic signal blockers as well as catalytic antioxidants prevent Ang-2 upregu-lation as well as diabetic pericyte loss in vivo.