Enzymatically inactive tissue-type plasminogen activator (EI-tPA) reverses colitis in mice exposed to 5% dextran sulfate sodium (DSS) for 7 days. A: Mice were exposed to 5% DSS in the drinking water for 7 days and then injected intravenously once with EI-tPA (blue curve) or with vehicle (phosphate-buffered saline; orange curve). Control (Con) mice were not exposed to DSS (black curve). Weight was recorded and expressed as the percentage change compared with that recorded on day 0. B: Mice were exposed to 5% DSS for 7 days and then treated with EI-tPA or vehicle. Stool scores were determined on days 7, 9, and 13. C: Representative images of colons harvested from mice that were not DSS-exposed (Control), mice exposed to DSS for 7 days and then allowed to recover for 7 days (DSS), and mice exposed to DSS for 7 days, treated with EI-tPA on day 7, and then allowed to recover for 7 days (DSS + EI-tPA). D: Colon length results are summarized. E and F: Representative hematoxylin and eosin (H&E)–stained sections of colons from mice exposed to 5% DSS for 7 days, injected with vehicle on day 7, and allowed to recover for 7 days (E) and from mice exposed to DSS, treated with EI-tPA, and then allowed to recover for 7 days (F). The arrowheads indicate distal ends of the colon sections. Boxed areas are shown at higher magnification in the insets. G and H: H&E sections of colons recovered from mice that were not DSS-exposed (Con), exposed to DSS, and exposed to DSS with subsequent EI-tPA treatment were scored for cellular infiltration and for epithelial changes in the distal 25% of the colon. Data are presented as means ± SEM (D, G, and H). n = 9 mice exposed to 5% DSS in the drinking water for 7 days and then injected intravenously once with EI-tPA or with vehicle (A); n = 7 control mice not exposed to DSS (A); n = 7 (D). ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, and ∗∗∗∗P < 0.0001 DSS versus DSS + EI-tPA; †P < 0.05, †††P < 0.001, and ††††P < 0.0001. Scale bars: 1 cm (C); 10 μm (E and F, main images); 2 μm (E and F, insets).