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The blood-retinal barrier (BRB) is a well-recognized mechanism that underlies the retina’s immunological privilege. The BRB is formed locally by inhibitory molecules that bind to cell membranes, as well as by the suppression of systemic immune responses. Recent studies have revealed that microglial cells are essential for maintaining immunological privilege within the retina by regulating the immune response. They achieve this by enhancing or reducing ocular inflammation. Furthermore, retinal pigment epithelium (RPE) regulates the behavior of immune cells within the retina, which can lead microglial cells to reduce inflammation and promote immunological tolerance. With the aim of better understanding the biology of immunological processes within the retina, this article reviews the BRB and discusses the factors, systemic immune responses, microglia, RPE, and their associated enzymes that enable the BRB.