Effects of low-flow ischemia and reperfusion of the large colon on mucosal architecture were determined in horses. Twenty-four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline values. Systemic hemodynamic and metabolic variables were maintained constant and in a normal physiologic range. Full-thickness biopsy specimens were obtained from the left ventral colon for histomorphologic and morphometric examination at baseline and at 30-minute intervals for 6 hours; additional biopsy specimens were collected at 185, 190, and 195 minutes (corresponding to 5-, 10-, and 15-minute periods of reperfusion in group-3 horses). There were no differences among groups at baseline or across time in group-1 horses for any of the histopathologic variables. There were significant (P < 0.05) increases in percentage of surface mucosal disruption, estimated and measured percentage depth of mucosal loss, mucosal hemorrhage, mucosal edema, and cellular debris index during 0 hour to 3 hours, compared with baseline, and from 3 hours to 6 hours, compared with 3 hours in horses of groups 2 and 3. Estimated percentage depth of mucosal loss and cellular debris index were significantly (P < 0.05) greater in group-3 horses, compared with group-2 horses during the interval from 3 to 6 hours. There were trends toward greater percentage of surface mucosal disruption and mucosal edema during the early phase of reperfusion (3 to 4 hours) and greater mucosal hemorrhage, measured percentage depth of mucosal loss, and mucosal interstitial-to-crypt ratio during the late phase (4 to 6 hours) of reperfusion in group-3 horses vs group-2 horses. Reestablishment of colonic arterial blood flow after low-flow ischemia caused greater mucosal injury than did a comparable period of continued ischemia. Thus, reperfusion injury was detected in the large colon of horses after low-flow arterial ischemia. The serial mucosal alterations that developed in the colon were comparable in horses of groups 2 and 3; however, reperfusion exacerbated colonic mucosal injury.