Inflammation and oxidative stress are involved in neovascular retinopathies (NR). Nitro-fatty acids are important electrophilic signaling mediators with anti-inflammatory and cytoprotective properties (Keap1/Nrf2 pathway). Here, we hypothesized that Nitro-oleic acid (NO2-OA) modulates the antioxidant response and has a cytoprotective effect in NR. An Oxygen-Induced Retinopathy (OIR) mouse model was used. OIR mice were intraocular (i.o.) injected at P12 with 5 μM of NO2-OA or vehicle and intraperitoneal (i.p). at P14, P17, P20, P23 with 15 mg/Kg of NO2-OA or vehicle. At P17 or P26 mice were sacrificed. Some eyes were fixed to obtain whole mount for microscopy and other retinas were used for Western blot or RT-PCR assays. The electrical activity of the retina in response to a light stimulus was measured by scotopic electroretinography (ERG). Amplitudes and latencies of a- and b-waves from scotopic ERG were recorded at P17 y P26. Whole mounts showed that NO2-OA induced the vascular regrowth and decrease the pathological neovascularization at P17. In addition, Western blot of neural retinas showed significant changes in proteins involved in neurotoxicity and stress glial (GS and GFAP) at P17 in OIR mice treated with NO2-OA respect to vehicle. At P26 NO2-OA prevented the decrease in b-wave amplitude as well as the diminished expression of total Caspase-3 protein in P26 OIR. These findings suggest that NO2-OA could be beneficial or cytoprotective for retinal cells in NR.