Objective Neuronal cell death, glial cell activation, retinal swelling and oxidative injury are complications in retinal ischemia/reperfusion (I/R) injuries.Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are good for "eye health" in Chinese medicine.The aim of our present study is to explore the use of LBP in retinal I/R injury.Methods Retinal I/R injury was induced by surgical occlusion of the internal carotid artery.Prior to induction of ischemia, mice were fed orally with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week.Ischemia was maintained for 2 hours and reperfusion was then allowed for 22 hours.Paraffin-embedded retinal sections were prepared.Viable ceils were counted while apoptosis was assessed using TUNEL assay.Expression levels of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), poly (ADP-ribose) (PAR) and nitrotyrosine (NT) were investigated by immunohistochemistry.The integrity of blood-retinal barrier (BRB) was examined by IgG extravasation experiment.Results Decreased viable cell count and apoptosis were found in the ganglion cell layer (GCL) and the inner nuclear layer (INL) of the vehicle-treated I/R retina.Additionally, increased retinal thickness, GFAP activation, AQP4 up-regulation, IgG extravasation and PAR expression level were observed in the vehicletreated I/R retina.Most importantly, many of these changes were diminished or abolished in the LBP-treated I/R retina.Conclusion Pre-treatment with LBP for 1 week effectively protected the retina from neuronal death, apoptosis, glial cell activation, aquaporin water channel up-regulation, disruption of BRB and oxidative stress.The present study suggests that LBP may have a neuroprotective role in ocular diseases in which I/R is a feature.