AbstractNine normal and 24 diabetic subjects were examined by long‐term vitreous and plasma fluorescein fluorophotometry and the observed concentration profiles were described by biexponential time courses. The rate constant of elimination of fluorescein from the body (K10) was significantly decreased in diabetics with background and proliferative retinopathy, presumably caused by affection of the liver and possibly representing alterations in membranes of liver cells. Increased kidney albumin excretion was observed with increasing degree of retinopathy. The apparent rate constant of fluorescein penetration into the eye (Kin) was found significantly decreased in background as well as in proliferative retinopathy; while the permeability index, calculated as areas under vitreous and plasma fluorescein curves, was significantly increased. In the normal subjects Kinwas significantly higher than the rate constant of fluorescein transfer (K12) from the apparent central to the peripheral tissue compartment, whereas in the diabetics this difference was only found in the group with background retinopathy. The findings seem compatible with the concept that the breakdown of the blood‐ocular barrier could be caused at least partly by affection of an active transport system for fluorescein, but thickening and compositional changes of the basement membranes in the eye might also be of importa