Purpose: To better characterize the role of proteoglycans in scleral tissue remodeling during the development of minus lens induced myopia and during recovery in tree shrews. Methods: Competitive reverse-transcription polymerase chain reaction (RT-PCR) was used to quantify the scleral mRNA levels for aggrecan, decorin, biglycan, and lumican in a group of tree shrews following four days of monocular-5 D lens treatment (n=5) and in a group after two days of recovery after 11 days of -5 D lens wear (n=5). Values were compared with age-matched normal animals (n=5). Aggrecan was localized within the sclera using immunohistochemistry. Results: Four days of -5 D lens wear produced axial (vitreous chamber) elongation and a myopic shift in the treated eyes. Two days of recovery produced significant refractive recovery. Aggrecan mRNA levels showed differential, bidirectional regulation. Levels in the treated eye sclera relative to the control eye were 30.8%±2.4% lower after four days of -5 D lens treatment and 51.4%±2.4% higher after two days of recovery. Decorin, biglycan, and lumican mRNA levels showed little differential regulation. However, biglycan and lumican along with aggrecan showed binocular regulation (treated and control eye mRNA levels significantly lower than normal eye mRNA levels after 4 days of -5D lens treatment). Immunohistochemical results showed that aggrecan is present in tree shrew sclera and that it is located primarily between the collagen lamella and near the fibroblasts. Conclusions: These data suggest that the expression of aggrecan is strongly differentially modulated in the sclera during experimentally induced myopia and recovery. The modulation of aggrecan in concert with previously described changes in type I collagen and hyaluronan may play a key functional role in modulating the ability of the lamellae to slip across one another. This may be manifested in the scleral creep rate, which in turn modulates axial elongation rate and refractive state. © 2007 Molecular Vision.