Angiotensin II (AII) influences Na⁺ and fluid transport across the small intestine, an effect mediated by AT1 and AT2 receptors. The observation that AII inhibits Na⁺-dependent (SGLT-mediated) glucose transport in renal cells (Kawano et al. 2002; Han et al. 2003) raises the issue of whether AII affects enterocyte sugar transport. Of further interest is the possibility of local secretion and action of AII, since components of an intrinsic renin-angiotensin system (RAS) have been detected in jejunal mucosa (Cox et al. 1986; Duggan et al. 1989). The aims of our present study were to determine whether a local RAS is expressed in enterocytes per se, and to examine the influence of AII on glucose uptake across the luminal membrane. Protein and mRNA expression of RAS components in villus enterocytes isolated from rat jejunal and ileal sections were measured using Western blotting and real-time PCR. Mucosal uptake of ¹⁴C-glucose was determined using everted jejunal sacs with or without AII (0-100 nM) in the mucosal fluid. Gene expression of angiotensin converting enzyme (ACE), angiotensinogen (AO), AT1 and AT2 receptors was detected in enterocytes, mRNA levels for AO, AT1 and AT2 receptors being 3.3-, 3.6- and 3.3-fold, respectively, greater in ileal compared to jejunal cells. Ileal:jejunal expression of AT1 and AO protein was 1.6 and 2.6, respectively. Immunocytochemistry revealed that AT1 receptors were expressed at both brush border and basolateral membranes. Phlorizin, a blocker of SGLT-mediated glucose transport, inhibited glucose uptake. The addition of AII to the mucosal fluid rapidly (within 2 min) also suppressed jejunal glucose uptake (12.0±0.4 and 2.8±0.1 nmol glucose/mg dry weight/min at AII = 0 and 100 nM, respectively, p<0.001 Student's unpaired t test), an effect that was dose dependent and which could be abolished by adding the AT1 receptor antagonist Losartan (1 µM) to mucosal fluid. Our detection of an enterocyte RAS, together with the finding that AT1-receptor stimulation at the brush border membrane suppressed glucose uptake implies a hitherto unrecognized system for regulation of intestinal glucose transport. The higher RAS expression in ileum compared to jejunum may indicate differential inhibitory effects of the RAS system on glucose uptake in the two regions.