Topical and systemic steroid delivery is a very effective treatment for many ocular conditions but is compromised by raised intraocular pressure which in turn leads to death of retinal ganglion cells and irreversible blindness. This is an important consideration with intraocular steroid release devices. Steroid-induced hypertension is associated with increased extracellular matrix deposition in the trabecular meshwork inhibiting outflow of aqueous humour. Resveratrol is a polyphenol found in grapes, wine and other plants. It has been linked to protective effects in heart disease and diabetes, and extending lifespan, due to antioxidant properties, although evidence in humans is not yet available. Previous studies by the authors have shown that a single topical treatment of trans-resveratrol in rats with steroid induced ocular hypertension (SIOH) reduced ocular hypertension. This was shown to be due to activation of adenosine A1 receptors and possible matrixmetalloproeinase-2 activity. In this study, trans-resveratrol topical administration was given twice daily, bilaterally to rats with or without SIOH. Treatment with trans-resveratrol significantly reduced IOP in animals with SIOH, associated with increased aqueous humour MMP-2 levels. TM thickness and cell number was reduced in treated animals, and the ganglion cell layer and inner retinal thickness were significantly increased. Finally, retinal oxidative stress was significantly decreased by treatment. These results support the use of trans-resveratrol in SIOH with positive effects on both the anterior and posterior segments of the eye.