Retinal capillary degeneration occurs following retinal neuronal cell degeneration. In this study, we examined effects of inhibitors of matrix metalloproteinase (MMP)-9 on neuronal cell loss and capillary degeneration in a neonatal rat model of NMDA-induced retinal neurotoxicity. Intravitreal injection of NMDA (50 or 200 nmol) was performed on postnatal day (P) 7 and morphological changes in retinal neurons and vasculature were examined on P14. The MMP inhibitor CP101537 (100 nmol) or vehicle (DMSO) was intravitreally injected simultaneously with, or 2 days after NMDA injection. CP101537 protected against neurovascular degeneration in a time-dependent manner as follows: 1) simultaneous injection of CP101537 with NMDA prevented retinal neuronal loss induced by NMDA (50 nmol), and 2) capillary degeneration in NMDA (200 nmol)-treated retinas was suppressed when CP101537 was injected 2 days after NMDA treatment. Gelatin zymography and Western blot analyses indicated that the activity and protein levels of MMP-9 were enhanced in the retina from 4 h to 2 days after NMDA injection. These results suggest that MMP-9 inhibitors may have therapeutic potential in treatment of retinal neurovascular degenerative diseases.