We investigated the therapeutic effect of vitamin D3 in a rat diffuse axonal injury model. A total of 60 male Sprague-Dawley rats weighing 175-200 g were anaesthetized and subjected to head trauma using Marmarou's impact-acceleration model. The rats were then separated into two groups; one group was treated with vitamin D3 and the other with saline for up to 4 days after the head trauma. Rats from both groups were killed 1, 3 or 8 days post-injury. The brains were examined histopathologically and scored according to the level of neuronal, vascular and axonal damage. There were no significant differences between the groups after 1 or 3 days, but evaluation after 8 days revealed a significant improvement in the group treated with vitamin D3. Our data indicate that vitamin D3 has a beneficial effect in diffuse axonal injury and may be useful in the management of this condition.