The purpose of this study was to investigate the neuroprotective potential of submicron (milled) and blended Lycium barbarum (LB) in glaucomatous retinal neuropathy using a rat model of high intraocular pressure (HIOP) induced retinal ischemia. The rats were treated with 500, 250, 100 mg/kg LB (submicron or blended form) orally once daily for 56 days respectively after 1 week of retinal ischemia induction. We conducted electroretinography (ERG), histopathological analysis in retina and antioxidative level assays, such as total glutathione (GSH (glutathione) + reduced glutathione) + GSSH (glutathione disulfide), catalase activity, SOD (superoxide dismutase) activity, and lipid peroxidant malondialdehyde (MDA) in the retina and plasma of test rats. The results indicated that the amplitudes of a and b wave of ERG were preserved in rats treated with submicron and blended LB groups, the best protective effect on ERG b wave amplitudes was observed at the dosage of 250 mg/kg of both forms of LB. Retinal thickness was best preserved, particularly significant in the retinal inner nuclear layer in submicron 250 mg/kg LB group. The levels of antioxidant GSSH+GSH, SOD and catalase activity in the retina were higher in blended 500 mg/kg and submicron 250 mg/kg groups than other groups, while the MDA level was lower in submicron LB groups than that in blended LB and non-LB IR group. In the plasma, there was no significant difference in the levels of GSSH+GSH and catalase activity between treated groups, but higher levels of SOD and lower levels of MDA were observed in 250 mg/kg submicron and 500 mg/kg submicron LB groups than the blended LB and non-LB IR groups. Generally better antioxidative effects were observed in the submicron LB than blended LB among treated groups, especially the 250 mg/kg submicron LB, providing good retinal neuroprotection by preserving retinal structure and function with improved antioxidative capacity. The submicron LB may have clinical implication as an adjuvant therapy of oxidative stress and retinal damage caused by HIOP induced retinal ischemia and reperfusion injury.