PURPOSE To analyze morphologic changes in the trabecular meshwork (TM) of bovine eyes treated with topical prednisolone and exhibiting elevated intraocular pressure for 4 weeks. METHODS The TM of four adult Braford cow eyes treated with 0.5% prednisolone eye drops three times daily for 7 weeks and their contralateral eyes treated with artificial tear preparation and that of two adult untreated Braford cows and untreated young calves eyes were analyzed with light and electron microscopy. Increased extracellular matrix (ECM) under the outflow loops was evaluated quantitatively. Additionally, deparaffinized tissue of treated eyes was labeled with an antibody against type VI collagen for immunocytochemistry. RESULTS In steroid-treated eyes ECM (plaques) accumulated under the endothelium of the inner wall of the outflow loops. On electron microscopy, this material contained fine fibrils that labeled for type VI collagen. Plaques were also seen in the contralateral controls of the treated animals but here they were significantly less in amount. In the untreated Braford controls and in untreated calf eyes, plaques were nearly absent. In the TM cells of the treated eyes there was a loss of glycogen from the cytoplasm and an increase in basement membrane-like material. These changes were not seen in contralateral eyes or eyes of untreated animals. CONCLUSIONS Accumulations of ECM in the treated eyes resembled morphologic changes in human eyes with primary open-angle glaucoma and steroid-induced glaucoma. This animal model, therefore, provides a good tool in which to further study the pathogenesis of TM changes in glaucoma.