Glucocorticosteroids (CGs) are widely used to reduce macular edema of any origin. GCs induce a quick (within hours) reduction in macular thickness, not well correlated to vascular leakage. Kinetic of action suggests that GCs are involved in fluid elimination from the retina but their mechanisms of action remain poorly understood. GCs act through activation of gluco and mineralocorticoid receptors that are co-expressed in retinal cells such as retinal glial Muller cells and retinal pigment epithelial cells, both involved in hydro-ionic balance in the retina. Through binding to either gluco and/ or mineralocorticoid receptors, CGs exert a direct regulation of ions and water movement through expression and distribution regulation of Kir 4.1, ENac and AQP4 channels in retinal glial Muller cells. Depending on their differential affinity for gluco or mineralocorticoid receptors and depending on the dose, different GCs act differently on hydro ionic regulation. These findings open new insight in the mechanisms of action of GCs on retinal edema and suggest that a more rationale use of GCs could help optimize the ratio efficacy/side-effects of GCs.