Post-surgical macular oedema results from blood-retinal barrier breakdown, but it is not accompanied by structural abnormalities in the retinal vessels or retinal pigmented epithelium. Previous studies, using horseradish peroxidase in a primate model, suggested that leakage occurs primarily through this epithelium. This study was conducted to localize sites of the barrier breakdown in humans following different types of intra-ocular surgery and to compare them with eyes affected with ocular inflammatory disease, ocular infection, and choroidal melanoma. Paraffin sections of eyes were immunohistochemically stained for albumin to localize extravascular albumin, which was graded in a masked study. With aphakia/pseudophakia, penetrating keratoplasty, ocular inflammatory disease, ocular infection, and choroidal melanoma, barrier breakdown occurred primarily at the inner blood-retinal barrier (retinal vasculature), but leakage also occurred at the outer barrier (retinal pigmented epithelium). After retinal re-attachment surgery, the inner and outer blood-retinal barriers were equally compromised. Vascular leakage in the optic nerve head coincided with barrier failure in these disorders. The widespread pattern of blood-retinal barrier compromise with leakage at multiple sites suggests that soluble mediators are likely to play a role in postsurgical macular oedema, ocular inflammatory disease, and choroidal melanoma.