Spinal cord injury (SCI) is a common spine surgical injury that leads to loss of activities of daily living. NEUROD2, a member of the neuroD family, is newly known to play a crucial role in SCI progression. We aimed to investigate the underlying mechanism wherein miR-153 and NEUROD2 modulate the process of SCI.Expression of miR-153 and NEUROD2 in spinal cord in mice of SCI were analyzed employing western blot and qRT-PCR assays. Microglial cells were transfected with mimic of miR-153 or siRNA targeting NEUROD2 to determine the impact of miR-153 and NEUROD2 on SCI induced inflammatory reaction and oxidative stress. A luciferase reporter assay was conducted to verify the regulation of miR-153 on NERUOD2.MiR-153 expression was decreased in injured spinal cord, while NERUOD2 was increased in a time-dependent manner. Addition of miR-153 mimic or silencing NERUOD2 might significantly inhibit the production of inflammation cytokines and attenuated oxidative stress in microglia cells of SCI. Luciferase reporter assay suggested that NERUOD2 was a direct target of miR-153.We proved that miR-153 attenuated inflammatory response and oxidative stress induced by SCI by targeting of NEUROD2, indicating a protective role in SCI progression.AJTR Copyright © 2021.