Escin, a natural mixture of triterpenoid saponins isolated from the seed of the horse chestnut (Aesculus hippocastanum), has been demonstrated to possess glucocorticoid (GC)‑like anti‑edematous and anti‑inflammatory effects. The aim of the present study was to investigate whether escin exhibits synergistic protective effects on blood‑retinal barrier (BRB) breakdown when combined with GCs in a rat model of retinal ischemia. Low concentrations of escin and triamcinolone acetonide (TA) alone did not affect BRB permeability. However, when administered together, low‑dose escin and TA significantly reduced BRB permeability following ischemia. Furthermore, low‑dose escin and TA alone did not affect the expression of occludin in the ischemic retina; however, when administered together, they significantly increased occludin expression in the ganglion cell layer of the ischemic retina. This indicates that escin and GCs have synergistic protective effects on BRB breakdown and the molecular mechanisms may be correlated with the upregulation of occludin. Therefore, the administration of escin may allow a reduction in the dose of GCs for the treatment of macular edema. The combination of escin with GCs is potentially a beneficial treatment method for BRB breakdown and warrants further investigation.