Aim of this study was to assess the structural,ultrastructural, immunohistochemical, and clinicalaspects in Sprague-Dawley rats with dextrane sulfatesodium (DSS)-induced colitis. Colitis was induced in Sprague-Dawley rats by seven days of DSSoral administration followed by seven days of tap wateronly (for one, two and three cycles). Controls were fedwith water only. Segments of proximal, mid-, and distal colon of each animal were adequatelyprepared for light and scanning electron microscopeobservations. The severity of the lesions was scoredhistologically. For immunohistochemical study, acocktail of S-100, NSE, and antineurofilament antibodieswas used. Symptoms such as weight, feces consistency,diarrhea, hematochezia were recorded daily. From aclinical point of view symptoms appeared significantly later after the first cycle than after thesecond and third cycles and lasted significantly longerin the second and third cycles. Treated rats showed aslower weight gain rate by 20% compared to controls, and the whole colon length appeared to besignificantly shorter after colitis induction comparedto controls. Structural observations by light microscopyshowed prominent involvement of the distal colon. Immunohistochemical study of both submucosaland myoenteric nerve plexuses was similar to controls.Scanning electron microscope observations of the colonicmucosal surface in colitis rats showed a complete subversion of its architecture, characterizedby dilatations of gland crypt openings, dropout ofgoblet cells, and inhomogeneous distribution or lack ofmicrovilli. These were most evident after the third cycle. In conclusion, experimental DSS colitisin SD rats appeared to be highly reproducible and sharedmost features with human UC, not only from a structuraland clinical but also from an ultrastructural point of view.