A major component of the damaging effect after traumatic brain injury (TBI) is activation of the inflammatory system. In particular, chemokines and chemokine-regulated factors become activated in resident brain cells and signal to different invading immune cells. For evaluation of the effect on invading cells 3 days after injury, mice were treated with a single initial dose of the anti-inflammatory agent Rabeximod in an experimental TBI model. For comparison, mice subjected to TBI were similarly injected with cyclophosphamide. TBI resulted in reduced body weight, an effect further enhanced by administration of Rabeximod, without obvious influence on motor performance. As revealed by quantitative RT-PCR, microglial upregulation of chemokine Ccl3 in response to TBI was unaffected by Rabeximod. Also, injury-induced expression of Cxcl10 in plasmacytoid dendritic cells (DCs) and endothelial expression of platelet selectin (Selp) were uninfluenced by Rabeximod. In contrast, Rabeximod robustly reduced the H2-Aa transcript characteristic for classical DCs defined by CD11c/Itgax in the injured brain. In addition, the expression of lysozyme 2 in large phagocytic cells was impaired by Rabeximod. These results show that Rabeximod exerts a selective and potent inhibition of cells serving cortical antigen presentation after brain trauma.