BACKGROUND: The contribution of brain edema to brain swelling in cases of traumatic brain injury (TBI) remains a critical problem. We believe that inflammatory reactions may play a fundamental role in brain swelling following a head injury. Although possible roles of microglia activation and the release of mediators have been suggested, direct evidence of cellular immune reactivity in diffuse brain injury following closed head trauma is lacking. Accordingly, the objective of this study was to assess the temporal pattern of microglia activation and lymphocyte migration in an experimental model of TBI. METHOD: An impact acceleration TBI model was utilized to induce diffuse brain damage in adult Wistar rats. The animals were separated into three groups: unoperated controls, sham-operated controls and trauma group. At various times after TBI induction (5 min-24 h), rats were perfused transcardially. Sagittal brain sections were analyzed with immunohistochemical markers of CD3 to reveal the presence of T-lymphocytes, and by immunochemistry for the detection of CD11b to reveal microglia activation within the brain parenchyma. FINDINGS: In the control groups, scattered T-cells were found in the brain parenchyma. In the trauma group, TBI induced microglia activation and a transient biphasic T-cell infiltration of the brain parenchyma in all regions was found, beginning as early as 30 min post injury and reaching its maximum values at 45 min and 3 h after trauma induction. CONCLUSION: These results lead us to suggest that the acute response to severe head trauma with early edema formation is likely to be associated with inflammatory events which might be triggered by activated microglia and infiltrating lymphocytes. It is difficult to overestimate the clinical significance of these observations, as the early and targeted treatment of patients with severe head injuries with immunosuppressive medication may result in a far more favorable outcome.