Traumatic brain injury (TBI) has been regarded as one of the leading cause of injury-related death and disability . White matter injury after TBI is characterized by axon damage and demyelination, resulting in neural network impairment and neurological deficit . Brain-derived neurotrophic factor (BDNF) can promote white matter repair . The activation of peroxisome proliferator-activated receptor gamma (PPARÎ³) has been reported to promote microglia/macrophages towards anti-inflammatory state and therefore to promote axon regeneration . Bexarotene, an agonist of retinoid X receptor (RXR), can activate RXR/PPARÎ³ heterodimers . The aim of the present study was to identify the effect of bexarotene on BDNF in microglia/macrophages and axon sprouting after TBI in mice . Bexarotene was administered intraperitoneally in C57BL/6 mice undergoing controlled cortical impact (CCI). PPARÎ³ dependency was determined by intraperitoneal administration of a PPARÎ³ antagonist T0070907 . We found that bexarotene promoted axon regeneration indicated by increased growth associated protein 43 (GAP43) expression, myelin basic protein (MBP) expression, and biotinylated dextran amine (BDA) + axon sprouting . Bexarotene also increased microglia/macrophages-specific brain derived neurotrophic factor (BDNF) expression after TBI . In addition, bexarotene reduced the number of pro-inflammatory microglia/macrophages while increased the number of anti-inflammatory microglia/macrophages after TBI . Moreover, bexaortene inhibited pro-inflammatory cytokine secretion . In addition, bexarotene treatment improved neurological scores and cognitive function of CCI-injured mice . These effects of bexarotene were partially abolished by T0070907 . In conclusion, bexarotene promotes axon sprouting, increases microglia/macrophages-specific BDNF expression, and induces microglia/macrophages from a pro-inflammatory state towards an anti-inflammatory one after TBI at least partially in a PPARÎ³-dependent manner.