Background: The study of possible ways of effective correction of retinal ischemia-reperfusion injury, which accompanies a number of eye diseases, is relevant today. The aim of the study: To study the retinoprotective effect and antiapoptotic mechanism of 2-Ethyl-3-hydroxy-6-methyl-pyridine-N-acetyltaurinate (EHMP-NAT) in a rat model of retinal ischemia–reperfusion (I/R). Materials and methods: A pathology model with an increase in intraocular pressure (IOP) to 110 mmHg was used. The retinoprotective effect of EHMP-NAT at a dose of 4.4 mg/kg/day, in comparison with emoxipine and taurine in equimolar doses, was estimated by the changes in the retinal microcirculation, electroretinograms (the b/a coefficient), and retinal caspase-3, NF-κB p65, p53 gene expressions in Wistar rats. Results: The use of EHMP-NAT led to an increase in the retinal microcirculation level to 756.5 (median) perfusion units in comparison with emoxipine (p = 0.045) and taurine (p = 0.00029). The b/a coefficient increased in comparison with the group with emoxipine (p = 0.0099) and with the group with taurine (p = 0.015). In the group with EHMP-NAT, the caspase-3 gene expression decreased reliably in comparison with emoxipine (p = 0.0002) and with taurine (p = 0.0028); the NF-κB p65 gene expression decreased in comparison with emoxipine (p = 0.0009) and with taurine (p = 0.0022); the p 53 gene expression decreased in comparison with emoxipine (p = 0.0022) and with taurine (p = 0.0009).  Conclusion: Based on the data obtained, in correction of retinal I/R by EHMP-NAT, improvements in the retinal microcirculation, functional state, and caspase-3, NF-κB p65, p53 gene expressions were more pronounced than in monotherapy with emoxipine or taurine.