Objective To investigate the expression of Nogo-A in the retinal ganglion cells (RGCs) and their axons of mouse embryos and its time course changes. Methods Sections of retinofugal pathway of C57 mouse embryos at different developmental stages were immunostained with Nogo-A specific antibody and observed by a confocal microscopy. The identity of Nogo-A positive cells was partially revealed by doublestaining together with Tuj-1 Results At the early stage of E12, Nogo-A was densely expressed in some radiallyorientated cells in retina. The immunopositive signals appeared in the cytoplasm, on the cell membrane and axons. The double-labeling together with Tuj-1, a neuronal marker, showed that nearly all the RGCs and their axons expressed Nogo-A protein. At the later stage of E13, the number of Nogo-A positive neurons in retina decreased dramatically. And those Nogo-A positive RGCs were specifically located in the ventricular part and the ciliary margin zone of the retina. At this stage, only a very few axons maintained their Nogo-A expression in the fiber layer of the retina, while most lost their Nogo-A distribution. When most RGCs had fully differentiated at E15, there was no detectable Nogo-A immunopositive staining in the retina and only a few retinal fibers were Nogo-A immunopositive. The similar expression patterns of Nogo-A was found in a few axons along the optic disc, optic stalk, optic chiasm and optic tract. Worthy of note, the retinal axons with Nogo-A distribution in the optic tract were exclusively found in the superficial area, where the newly arrived axons were traveling through during development. Conclusion The expression pattern and its time course change suggested that Nogo-A was an important protein expressed by the newly differentiated RGC neurons and their projecting axons, whilst the mature RGCs down-regulated their expression. Nogo-A in the new born RGCs might play some cellintrinsic roles such as de