Abstract: Background and Objective: Studies report the beneficial effects of short-chain fatty acids on intestinal health, hyperglycemia and kidney disease. However, it is unknown whether tributyrin, a prodrug of butyric acid, produces the same effects. Due to the limitations of current treatments for patients with chronic diabetic disease, other alternative therapies could provide a better quality of life for the patient. Therefore, the objective was to evaluate the effect of tributyrin in an animal model with this pathology. Materials and Methods: Twenty-seven male Wistar rats weighing 200-250 g were assigned randomly into three groups. The animals received food and water ad libitum. The G1 and G2 animals were chemically induced into a model of chronic diabetes, with liver and kidney damage, using streptozotocin. At G1 and G3 (healthy animals): Tributyrin (Tb: 450 mg kg–1 PO SID) was administered for 4 weeks. To G2 (control group): Only physiological saline solution 4.5 mL kg–1 PO SID was given. Hemogram, blood biochemistry and urinalysis were performed at the beginning and every week. In addition, a glucose tolerance test was performed before and at the end of treatment. At the end of the study, histopathology examinations were performed. Results: Supplemented tributyrin increased insulin sensitivity, decreased blood glucose and improved liver and kidney tissue. Conclusion: Oral tributyrin supplementation in a rat model of chronic diabetes mellitus improved blood glucose levels, produced a hepatoprotective effect and delayed kidney disease. Therefore, tributyrin is considered a complementary therapy to the usual treatment of type 1 diabetes mellitus.