Abstract This study examined the time course of the blood–brain barrier (BBB) opening and correlated this with brain edema formation after a lateral controlled cortical impact (CCI) brain injury in rats. Quantitative measurement of Evans blue (EB) extravasation using fluorescence was employed at 2, 4, 6 h and 1, 2, 3, 4 and 7 days after injury. Brain edema was measured by specific gravity of the tissue at corresponding time points. Two prominent EB extravasations were observed at 4–6 h and 3-day after injury in the injury-site cortex and the ipsilateral hippocampus. Brain edema became progressively more severe over time and peaked at 24 h after injury and began to decline after day 3. These results suggest that there is a biphasic opening of the BBB after CCI brain injury and the second opening of the BBB does not contribute to a further increase in edema formation.