The β-adrenoceptor (β-AR) system has been implicated in the pathological angiogenesis of the retina. Of the three β-ARs, the role of β3-AR remains to be elucidated. In a mouse model of oxygen-induced retinopathy (OIR), we investigated the role of β3-ARs using the 129S inbred mouse strain, which is highly responsive to hypoxia because of its marked imbalance between pro- and anti-angiogenic factors. We found that β3-AR activation with BRL37344 and CL316243, both potent, first-generation β3-AR agonists promotes the revascularization of the central retina in association with the restored astrocyte template. Recovered vascularization of the central retina prevents the onset of hypoxia thus impeding the activation of the pro-angiogenic pathway and inhibiting neovessel overgrowth in the mid periphery, blood-retinal barrier leakage and retinal dysfunction. Vessel rescue and recovered astrocyte density were found to be associated with protective effects against the OIR-related loss of retinal ganglion cells (RGCs) as also demonstrated by their recovered functional activity. RGC rescue occurs in connection with restored availability of neurotrophic factors that are otherwise impaired under hypoxia. Results from microdissected astrocytes were indicative of the possibility that astrocytes might contribute to retinal rescue. β3-AR has emerged as a potential intermediary in hypoxia-dependent neovascularization, thereby providing a rationale for exploring the causality between astrocyte recovery and retinal rescue with the aim of underlining the therapeutic potential of β3-AR agonists in proliferative retinopathies.