The inner blood-retinal barrier is highly complex, dependent on a normally functioning retinal vascular endothelium and possibly adjacent perivascular cells. There are undoubtedly many different grades of barrier failure, and in the early stages an inbuilt compensatory mechanism may prevent significant fluid accumulation and delay associated structural and functional changes. In diabetes, early barrier failure may be a function of an increase in the rate of endothelial cell death and turnover, probably exaggerated by the early and widespread loss of the supporting cells and dilatation of the small blood vessels.