OBJECTIVE: Intestinal ischemia-reperfusion injury (I/R) is a common syndrome encountered in clinic following intestinal surgery, strangulated hernia, and shock. Hypertonic saline has been shown to prevent inflammatory tissue damages caused by I/R and regulate immunologic disorders in peripheral blood. However, the immunoregulatory effects of hypertonic saline on the small intestine response to intestinal I/R have not been reported. MATERIALS AND METHODS: To investigate this, we created the intestinal I/R model by clamping the superior mesenteric artery in Sprague-Dawley rats. After 1 hour of ischemia, the vascular clamp was removed, and either normal saline (0.9% NaCl, NS group) or hypertonic saline (7.5% NaCl, HS group) was administered through the tail vein (6 ml/kg). The CD4(+) and CD(8+), primarily T-lymphocytes subpopulation yielded from the intestinal tissues, were determined by immunohistochemistry. RESULTS: A pro-inflammatory cytokine, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB), a critical transcription factor for the TNF-α gene, were measured in the intestinal and lung tissues with ELISA. HS induced an increase in CD4(+) and CD8(+) T cells in the jejunum and ileum compared with the NS group. The levels of TNF-α and NF-κB in the intestinal and lung tissues were significantly decreased in the HS group compared with those of the NS group. CONCLUSIONS: HS treatment may ameliorate the tissue damage induced by intestinal I/R. This protective effect is possibly due to its ability to activate the CD4(+) and CD8(+) T-lymphocytes cells in the intestinal tissues and inhibit the intestinal I/R-induced expression of pro-inflammatory cytokines.