To investigate the role of epithelial cell apoptosis in the stress-related changes of intestinal mucosa barrier following traumatic brain injury. Sixty-four health male Wistar rats were divided randomly into two groups: (1) traumatic brain injury model group (n = 32), in which rats suffered from traumatic brain injury by Feeney's method; (2) control group (n = 32), rats suffered from sham operation. Each group were divided into four subgroups according 6 h, 12 h, 24 h, and 48 h after operation (n = 8, for each subgroup). Ileum tissue were taken to observed the damage of the intestinal mucosa under microscope and electron microscope. The early apoptosis rate of intestinal mucosal cells were analyzed with Annexin V-PI double stained and detected by flow cytometry. The intestinal mucosa were damaged and the intercellular space of intestinal mucosal were found increased in traumatic brain injury group. The early apoptosis rate of intestinal mucosal epithelial cells was significant increased in traumatic brain injury group than that in control group [6 h: (13.5 ± 3.7)% vs (6.1 ± 1.7)%, P < 0.05; 12 h: (66.1 ± 6.0)% vs (5.2 ± 1.1)%, P < 0.05; 24 h: (39.8 ± 4.8)% vs (8.4 ± 2.6)%, P < 0.05; 48 h: (7.5 ± 1.3)% vs (6.6 ± 0.5)%]. The increased early apoptosis rate of intestinal mucosal epithelial cells might contribute to the stress-damage of the intestinal mucosa barrier in early stage of traumatic brain injury.