Pathological myopia, as one of the leading causes of blindness, is characterized by excessive and progressive elongation of the eyeball with concomitant degenerative changes in the posterior segment of the eye. During the progressive distension of the posterior pole, the retina, choroid, and sclera are subjected to constant mechanical force, as a result of which, tissue remodeling occurs. Active remodeling of the sclera in myopia has been studied intensively. By comparison, retinal remodeling under mechanical stretching has attracted little attention, and further research is therefore required. In this study, we showed that constant mechanical stretching of rat retinal Müller cells for 24 h led to a significant increase in the intracellular matrix metalloproteinase-2 mRNA and protein levels. The extracellular secretory matrix metalloproteinase-2 protein levels and activity were also enhanced. These results suggest a possible novel molecular mechanism that would account for retinal remodeling in many ocular diseases in which the retina is often overstretched, such as pathological myopia and proliferative vitreoretinopathy.