To evaluate a new chronic glaucoma model produced by intracameral injection of dexamethasone-loaded poly lactic-co-glycolic acid microspheres (Dex-PLGA-Ms) over six months. Healthy rats received two injections (at baseline and Week 4) of Dex-PLGA-Ms into the anterior chamber of the right eye. Clinical signs and intraocular pressure (IOP) were weekly recorded. The structure of the retina and optic nerve was in vivo evaluated using optical coherence tomography (OCT) every two weeks and functionally using dark- and light-adapted electroretinography at 0–12–24 weeks. Histological studies were also performed. IOP progressively increased up to hypertension (23.22 ± 3.63 mmHg) in both eyes but did so later in left eyes. OCT quantified a decrease in full-thickness retina posterior pole (R), retinal-nerve-fiber layer (RNFL), and ganglion-cell layer (GCL) thickness up to 24 weeks. Right eyes showed higher neuroretinal thickness loss up to week 8. RNFL experienced the highest percentage thickness loss at the inferior-superior axis, while in GCL the inner sectors of the horizontal axis (Nasal-Temporal) suffered the greatest decrease in thickness. Retinal ganglion cell, photoreceptor, and intermediate cell functionality decreased over time. Increased deposition of collagen IV was also found in zonular fibers and the ciliary body. This work shows the usefulness of drug delivery systems, not to treat pathology but to induce it. Only two injections of Dex-PLGA-Ms in the anterior chamber of rat eyes were enough to progressively create ocular hypertension and subsequent functional and structural neuroretinal degeneration, at least over 6 months.