BACKGROUND AND AIM We have previously shown that angiotensin II (ANGII) plays an important role in the regulation of the apoptosis of intestinal epithelial cells (IECs). In this study, we investigated the pathway by which ANGII modulates apoptosis of the IECs. METHODS Epithelial cells (HT-29) were cultured; the ANGII receptor type-1 (AT1R) inhibitor (Losartan) and ANGII receptor type-2 (AT2R) inhibitor (PD123319) were used separately to block the ANGII receptor. Flow cytometry was used to detect the apoptosis of the IECs. In the in vivo study, Sprague-Dawley rats were divided into 4 groups: sham group, which received a ileum transection (n = 6); sham + angiotensin-converting enzyme inhibitor (ACE-I) group, which received a ileum transection, and lavage with ACE-I (enalaprilat 2 mg · kg⁻¹ day⁻¹) (n = 6); short bowel syndrome (SBS) group, which received a 70% mid-intestinal resection (n = 6); and SBS + ACE-I group, which received a 70% mid-intestinal resection, and lavage with enalaprilat (2 mg · kg⁻¹ day⁻¹) (n = 6). Sampling was done 10 days after surgery. The expression of ANGII receptors Bax and Bcl-2 was detected with immunofluorescence, real-time-polymerase chain reaction, and Western blot methods. RESULTS Massive small bowel resection led to a significant increase in epithelial cells apoptosis, and the addition of ACE-I to SBS rat significantly attenuated this increase in apoptosis. AT1R expression on intestinal mucosa surface decreased after small bowel resection. Pretreatment with the AT1R antagonist Losartan significantly attenuated the increase of epithelial cell apoptosis caused by ANGII administration. Moreover, the Bcl-2/Bax ratio was found to be increased in cells pretreated with Losartan, which indicates a proapoptotic role of AT1R in cultured HT-29 cell lines. CONCLUSIONS These findings suggest that ANGII plays an important role in the regulation of apoptosis of the IECs. AT1R may be of crucial importance for the modulation of intestinal EC apoptosis.