BACKGROUND: The aim of this study was to assess early morphological changes of the residual small intestine 30 days after application of Benzalkonium Chloride (BAC) in a rat model of short bowel syndrome (SBS). MATERIALS AND METHODS: Twenty nine Wistar rats (260 ± 20g) underwent 80% midsmall bowel resection with end to end anastomosis. In group 1 (n=14) BAC solution 0.1% was applied to a 2cm segment of jejunum, and in group 2 (n=15) normal saline was applied in a similar manner and the rats were sacrificed 30 days after operation. Specimens for histological examination were obtained initially and at sacrifice. RESULTS: In the BAC treated jejunal segment (group 1), a statistically significant increase (p< 0.05) was noted in villous height by 33.2%, in crypt depth by 26.4%, in muscle thickness by 26%, 109.6% in intestinal diameter, and 20% in total intestinal length, compared to group 2. CONCLUSIONS: BAC application to the serosal surface of rat’s jejunum in SBS is a simple method that within only 4 weeks can topically augment the natural adaptation process noticed following intestinal resection. Further research with a tapering technique performed in sequence is suggested, to prevent possible problems associated with pseudoobstruction in the long term.