The cellular pathomechanisms of spinal cord injuries are poorly understood. The glial scar may impede neuronal regeneration but its temporal development is still unknown. Triple-transgenic mice with fluorescent proteins (axons, astrocytes and microglia/MG labeled yellow/YFP, cyan/CFP and green/GFP) were imaged before and after performing discrete spinal cord lesions (20-40 mm diam. at L4). The lesions were re-inspected regularly for up to one year. Within minutes after the lesion, MG sent their processes toward the site of injury. During the next 24 hours surrounding MG cells migrated toward the lesion and accumulated and stayed there for about a week. This reaction decreased slowly during the next five months. Monocytes crossing the blood-brain barrier during the acute reaction and invading the lesion site were not found. Astrocytes were slowly activated and started to extend processes to the lesion after two days. A full-blown astroglial reaction engulfing the lesion site developed after a week and decreased within five months post injury. Within hours after the lesion, dissected axons formed bulbous debris which was partly engulfed by the lesion directed MG processes. Other axonal bulbs remained at the same place caudal to the lesion for weeks. In some cases, axonal sprouting was detected three months after injury. Initially, neuronal sprouts were often not straightly directed towards the lesion but later they crossed the site of injury, when the glial scar was almost dissipated. Comparatively performed mechanical injuries induced similar spatiotemporal cellular reactions. The combination of multi-cellular labeling with multiple time points imaging allowed for the first time to explore the time course of cellular responses to spinal cord injury. Detailed knowledge of the temporal behavior of the main cell types involved in the reaction to injury may provide valuable hints for a therapeutical approach to improve axonal survival and regeneration.