This study was conducted to characterize the effect of miR-155 overexpression on white matter sparing and lesion size following contusion injury of spinal cord in mice. 60 C57BL/6J wild-type and 60 B6.Cg miR-155 knockout mice were used to induce moderate to severe contusive spinal cord injury at T9 segment. All used mice were female, 8–20 weeks old and weighing 18+ gm. Mice were divided into two main groups; for Real-time reverse transcriptase polymerase chain reaction (RT-PCR) and histology, then subdivided into five subgroups; 1, 3, 7, 14 and 42 days after the contusion according to time point, each was compared to naive control group. Fresh and fixed tissue were taken from thoracic segments (lesion area) from all time points, dissected and then evaluated using RT-PCR and histology (Eriochrome stain), respectively. We identified significant upregulation of miR-155 at the lesion site by 3 days and continued up to 6 weeks after the injury. Following spinal cord injury, the miR-155 overexpression was accompanied with severe cord damage and less tissue repair while more white matter sparing and smaller lesion size were detected in miR-155 knockout group.