Introduction: Traumatic brain injury (TBI) is a serious medical condition that affects annually year more than 2 million people worldwide. This study was aimed to evaluate the effect of lipopolysaccharide (LPS) on the number of dark neurons induced by TBI in the parieto-temporal cortex. Materials and Methods:  LPS (0.1 and 0.5 mg/kg) was injected i.p. to rats 5 days before induction of TBI in the parieto-temporal cortex. Using toluidine blue staining, we evaluated the number of dark neurons in the hippocampus in sham and LPS preconditioned rats 4 and 12 hours after the trauma. Results: The increase in dark neurons was significantly higher after 4 h of trauma compared to 12 h after TBI. LPS preconditioning significantly decreased the mean number of dark neurons in the hippocampus. In LPS preconditioned rats the mean number of dark neurons was also significantly higher 4 hours after trauma compared to 12 h after TBI. Conclusion: These data indicate that hippocampal cellular damage produced during the first hours after induction of TBI. This cellular damage could be prevented by administration of LPS.