We have evaluated the spatial and temporal expression patterns of three protein tyrosine phosphatases (PTPs), receptor PTPalpha (RPTPalpha), striatal enriched phosphatase (STEP), and leucocyte common antigen-related phosphatase (LAR), in the retina and optic nerve (ON) of adult rats in which the crushed ON was either regenerating after retinal ganglion cell (RGC) stimulation with intravitreal peripheral nerve (PN) grafting or lens injury (LI), or not regenerating (no treatment). In intact adult rats, all three PTPs were expressed by RGCs and ON glia. In both the regenerating and non-regenerating models, a postlesion rise in RPTPalpha, STEP, and LAR expression occurred in the RGC somata and in the ON. However, for RPTPalpha and LAR in the RGCs, and for RPTPalpha, STEP, and LAR in the ON, this postlesion increase was attenuated in the regenerating versus the non-regenerating models. ON PTP expression changes were localized to glia in the proximal and distal stumps, and to macrophages and extracellular matrix of the glial scar at the lesion site. Interestingly, neither RPTPalpha, STEP, nor LAR localized to intact or regenerating axons. One explanation of these findings is that RPTPalpha and LAR may modulate RGC survival, and that RPTPalpha, STEP, and LAR may modulate axon growth.