This study investigated capillary blood flow (CBF) and pathomorphological alterations in the mucosa of different bowel segments at different times after disease onset in rats with colitis induced by either trinitrobenzensulfonic acid (TNBS) or mitomycin-C. CBF was determined by intravital microscopy using fluorescein-labeled erythrocytes. The histological degree of inflammation was assessed by a new scoring system. Severe acute histological changes were found in the distal colon 24 hr after induction of TNBS colitis (score: 8.9 ± 1.0). CBF was increased (2.9 ± 0.05 vs. 2.6 ± 0.04 nl/min in healthy controls). The histological alterations persisted until day 3 (8.5 ± 0.9) when CBF significantly decreased (1.8 ± 0.05 nl/min). After 15 days, moderate acute inflammation was still detectable histologically (5.4 ± 1.3), but CBF had returned to normal values. In mitomycin-C colitis, changes developed mainly in the proximal colon: After three days, there was mild inflammation (2.8 ± 1.2) with normal CBF (2.5 ± 0.1 nl/min). After seven days, the inflammation had increased (4.8 ± 1.1), while CBF had decreased (1.5 ± 0.06 nl/min). These changes persisted for six weeks (5.3 ± 0.7; 1.2 ± 0.05 nl/min). These data suggest that disturbed colonic microcirculation may play an important role in the pathogenesis of inflammatory bowel disease regardless of the histopathomorphological alterations.