This study was undertaken to evaluate the effect of simvastatin, a cholesterol-lowering agent, on vascular endothelial growth factors (VEGFs), nitric oxide (NO) levels and neuroprotection, in rats with experimentally induced traumatic brain injury (TBI). Forty Wistar albino rats were categorized into four groups: sham operated (S), trauma (T), trauma + vehicle (T + V) and trauma + simvastatin (T + S). The T, T + V and T + S groups were subjected to TBI. The T + V group was administered vehicle [ethanol:saline (1/2)] and the T + S group was administered 1 mg/kg of simvastatin 3 h after the injury insult. Blood and brain tissue specimens were obtained 24 h after the trauma to measure VEGFs and NO levels and perform histopathological examinations. The histopathological injury scores of brain tissues were significantly higher in the T group, and simvastatin significantly prevented brain injury in the T + S group. In the T group, significant increases of VEGF levels in serum and brain tissues were noted, which were prevented with simvastatin treatment in the T + S group. The markedly high levels of NO in brain tissues of the T group were decreased by simvastatin treatment in the T + S group. It can be concluded that, as evidenced by histopathological findings, simvastatin treatment improves neuropathology in acute stages of TBI.