Rats are becoming an increasingly popular model system for understanding mechanisms of optic nerve injury in primary open-angle glaucoma (POAG). Although the anatomy of the rat optic nerve head (ONH) is different from the human, the ultrastructural relationships between astrocytes and axons are quite similar, making it likely that cellular processes of axonal damage in these models will be relevant to human glaucoma. All of these models rely on elevating intraocular pressure (IOP), a major risk factor for glaucoma. Methods that produce increased resistance to aqueous humor outflow at the anterior chamber angle, specifically hypertonic saline injection of aqueous outflow pathways and laser treatment of the limbal tissues, appear to produce a specific regional pattern of injury that may have a particular relevance to understanding regional injury in human glaucoma. Because increased pressure fluctuations are a characteristic of such models and the rodent ONH appears to have high susceptibility to elevated IOP, special instrumentation and measurement techniques are required to document pressure exposure in these eyes and understand the pressure levels that the eyes and the optic nerve are exposed to. With these techniques, it is possible to obtain an excellent correlation between pressure and the extent of nerve damage. Continued use of these models will lead to a better understanding of cellular mechanisms of pressure-induced optic nerve damage and POAG.