The purpose of this study was to evaluate the effect of female sexual hormones on intestinal and serum cytokines following traumatic brain injury (TBI). Adult female rats were ovariectomized and distributed among the following 9 groups: (i) sham trauma, (ii) TBI (Marmarou's method), (iii) vehicle (dimethylsulfoxide) treated, (iv) estrogen (E2) treated, (v) progesterone (P) treated, (vi) treated with E2+P, (vii) propylpyrazole triol (PPT) treated, (viii) diarylpropionitrile (DPN) treated, and (ix) control. PPT and DPN are estrogen receptor αand β agonists, respectively. Serum and intestinal levels of interleukin (IL)-1β were increased by TBI (P < 0.001). The level of intestinal IL-1β was increased in the group treated with E2 (P < 0.001). There was a reduction in serum IL-1β (P < 0.01) and an increase in intestinal IL-1β level (P < 0.001) in the PPT-treated group compared with the vehicle-treated group. TBI reduced serum IL-6 (P < 0.01) and increased intestinal IL-6 (P < 0.001). Serum IL-6 was increased in the group treated with E2 (P < 0.001), P (P < 0.001), E2+P (P < 0.01), and DPN (P < 0.001) after TBI; however, intestinal IL-6 was higher in the E2-treated group compared with the vehicle-treated group (P < 0.01). Intestinal tumor necrosis factor α (TNF-α) was increased by TBI (P < 0.001). Progesterone decreased serum TNF-α (P < 0.01). Intestinal TNF-α in the E2 (P < 0.01), E2+P (P < 0.001), and PPT (P < 0.001) treatment groups was less than in the vehicle-treated group. In conclusion, estrogen influences the intestinal levels of proinflammatory cytokines, in particular TNF-α, mediated through estrogen receptor α.