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Abstract Diabetic-metabolic syndrome (MetS-D) has a high prevalence worldwide, in which an association with the rupture of the intestinal epithelium barrier function (IEBF) has been pointed out, but the functional and morphological properties are still not well understood. This study aimed to evaluate the impact of acute hyperglycemia diabetes on intestinal tight junction proteins, metabolic failure, intestinal ion and water transports, and IEBF parameters. Diabetes was induced in male Rattus norvegicus (200-310 g) with 0.5 mL of streptozotocin (70 mg/kg). Glycemic and clinical parameters were evaluated every 7 days, and intestinal parameters were evaluated on the 14th day. The MetS-D animals showed a clinical pattern of hyperglycemia, with increases in the area of villi and crypts, lactulose:mannitol ratio, myeloperoxidase (MPO) activity, and intestinal tissue concentrations of malondialdehyde (MDA), but showed a reduction in reduced glutathione (GSH) when these parameters were compared to the control. The MetS-D group had increased secretion of Na+, K+, Cl-, and water compared to the control group in ileal tissue. Furthermore, we observed a reduction in mRNA transcript of claudin-2, claudin-15, and NHE3 and increases of SGLT-1 and ZO-1 in the MetS-D group. These results showed that MetS-D triggered intestinal tissue inflammation, oxidative stress, complex alterations in gene regulatory protein transcriptions of intestinal transporters and tight junctions, damaging the IEBF and causing hydroelectrolyte secretion. Diabeticmetabolic Diabetic MetSD MetS D (MetS-D worldwide (IEBF out understood proteins failure transports 200310 200 310 (200-31 g 05 0 5 0. 70 (7 mg/kg. mgkg mg/kg . mg kg mg/kg) days th day crypts lactulosemannitol lactulose mannitol ratio MPO (MPO activity MDA, MDA , (MDA) GSH (GSH Na Na+ K K+ Cl, Cl Cl- Furthermore claudin2, claudin2 claudin 2, 2 claudin-2 claudin15, claudin15 15, 15 claudin-15 NHE SGLT1 SGLT 1 SGLT- ZO1 ZO ZO- inflammation stress junctions 20031 20 31 (200-3 ( (MDA claudin- claudin1 claudin-1 2003 3 (200- (200 (20 (2