Traumatic brain injury is a major health problem with much of its morbidity associated with traumatic axonal injury (TAI). To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the specific anterograde and retrograde sequelae of TAI are poorly understood because the diffuse nature of TAI complicates data analysis. To overcome this limitation, we subjected transgenic mice expressing yellow fluorescent protein (YFP) within the visual system to central fluid percussion injury, and consistently generated diffuse TAI within the optic nerve that could easily be followed in the organized YFP positive fibers. We demonstrated progressive axonal swelling, disconnection and proximal and distal axonal dieback, with regression and reorganization of the proximal swellings, and the persistence of the distal disconnected and degenerating swellings. Antibodies targeting the C-terminus of amyloid precursor protein, a marker of TAI, mapped to the proximal axonal segments without distal targeting. Antibodies targeting microglia/macrophages, revealed activated microglia/ macrophages closely encompassing the distal disconnected, degenerating axonal segments at 7 - 28 days post injury, suggesting their role in the delayed axonal degeneration. In contrast, in the proximal reorganizing axonal segments, microglia/macrophages appeared less reactive with their processes paralleling preserved axonal profiles. Concomitant with these events, YFP fluorescence quenching also occurred, complicating data analysis. This quenching mapped to Texas-Red-conjugated-IgG immunoreactive loci, suggesting that blood–brain barrier disruption and its attendant edema participated in fluorescence quenching. This was confirmed through antibodies targeting endogenous YFP, which identified the retention of intact axons despite YFP fluorescent loss. Paralleling these events, TAI was not accompanied by retrograde retinal ganglion cell (RGC) death. Specifically, no TUNEL+ or cleaved caspase-3 immunoreactive RGCs were observed from 2 days to 3 months post-TBI. Further, Brn3a immunoreactive RGC quantification revealed no significant RGC loss. This RGC preservation was accompanied by the persistent phospho-c-Jun expression for up to 3 months post-TBI, a finding linked to neuronal survival and potential axonal repair. Parallel ultrastructural study again failed to identify RGC death. Collectively, this study provides unprecedented insight into the evolving pathobiology associated with TAI, and offers advantages for future studies focusing on its therapeutic management and neuronal reorganization.