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Retinal ischemia is a common cause of visual impairment for humans and animals. The neuroprotective effects of lidocaine (LDC) and methylprednisolone (MP) upon retinal ischemic injury were investigated in a rat model. Sprague-Dawley rats were divided into 3 groups, the IR control, LDC and MP. A very high intraocular pressure (HIOP) and retinal ischemia were induced. In LDC group, LDC bolus (1.5 mg/kg) was i.v. injected 30 min before ischemia and then a constant rate infusion (CRI) with 2 mg/kg/hr was given until 60 min after reperfusion. In MP group, MP bolus (30 mg/kg) was i.v. administered twice at 2 min before and immediately after ischemia, respectively. The HIOP damage to retina was evaluated by electroretinogram (ERG) and morphometrical histology. The functional analysis of the retina by ERG revealed a 35.2% reduction of a-wave in the IR group, 49.7% reduction in the LDC group but no significant change in the MP group compared to normal controls. An 81.0% reduction of b-wave was observed in the IR group, 80.7% reduction in the LDC group and 17.6% reduction in the MP group. In the morphometrical histology, the retinal inner plexiform layer/outer nuclear layer (IPL/ONL) ratio was reduced to 48.8% in the IR group, 80.1% in the LDC group and 96.2% in MP group. In conclusion, the MP showed significantly good neuroprotective effects on retinal IR injury, and the LDC showed moderate neuroprotective effects demonstrated in retinal structure but not in retinal function.