The short chain fatty acid (SCFA) butyrate provides energy for colonocytes, stimulates colonic fluid and electrolyte absorption and is recognised as an effective treatment for multiple types of colitis. To examine the impact of butyrate enema therapy on the clinical course, severity of inflammation, and SCFA stimulated Na+ absorption in a chronic experimental colitis. Distal colitis was induced in rats with a trinitrobenzenesulphonic acid (TNBS) enema. Five days after induction, rats were divided into groups to receive: no treatment, saline enemas, or 100 mM Na-butyrate enemas daily. On day 24, colonic damage score and tissue myeloperoxidase (MPO) activity were evaluated. Colon was mounted in Ussing chambers and Na+ transport and electrical activities were measured during a basal period and after stimulation with 25 mM butyrate. In the untreated and the saline enema treated TNBS groups, diarrhoea and extensive colonic damage were seen, associated with increased tissue MPO activities and absent butyrate stimulated Na+ absorption. In contrast, in the butyrate enema treated TNBS group, diarrhoea ceased, colonic damage score improved, and tissue MPO activity as well as butyrate stimulated Na+ absorption recovered to control values. Butyrate enema therapy stimulated colonic repair, as evidenced by clinical recovery, decreased inflammation, and restoration of SCFA stimulated electrolyte absorption.