Background:　The　differential　diagnosis　of　acute　and　chronic　colitis　remains　a　common　clinical　problem.　Optical　coherence　tomography　(OCT)　is　a　non-invasive,　high-resolution　imaging　technique　that　can　be　used　to　measure　morphological　changes　in　the　intestinal　wall　and　estimate　intestinal　inflammation.　We　aimed　to　conduct　an　ex　vivo　experiment　on　a　mouse　model　investigate　the　value　of　OCT　as　a　tool　for　the　differential　diagnosis　of　acute　and　chronic　colitis.　Methods:　Mice　were　administered　dextran　sulfate　sodium　salt　(DSS)　to　construct　acute　and　chronic　colitis　models.　Acutely-　and　chronically-affected　intestinal　walls　were　scanned　by　OCT,　and　then　the　scanned　colonic　tissue　samples　were　stained　with　hematoxylin　and　eosin　(HE).　Structural　and　morphological　changes　indicating　inflammation　in　the　intestinal　wall　were　evaluated　in　the　HE　sections　and　OCT　images　using　different　parameters.　The　parameters　were　used　in　one-way　analysis　of　variance　(ANOVA)　to　screen　for　a　differential　diagnosis　of　acute　or　chronic　colitis.　Results:　For　the　HE　sections,　the　angle　of　the　mucosal　folds,　length　of　the　basilar　part,　and　submucosal　height　and　area　were　statistically　significant　parameters　in　the　comparisons　between　the　mice　with　acute　colitis　and　the　control-group　mice　(P＜0.05).　In　the　comparisons　between　chronic　colitis　mice　and　control-group　mice,　the　angle　of　the　mucosal　folds,　length　of　the　basilar　part,　submucosal　height　and　area,　muscularis　thickness,　submucosal　height　+　muscularis　thickness,　and　mucosal　thickness　were　statistically　significant　parameters　(P＜0.05).　Finally,　in　the　comparisons　between　acute　colitis　mice　and　those　with　chronic　colitis,　the　angle　of　the　mucosal　folds,　submucosal　height　and　area,　muscularis　thickness,　submucosal　height　+　muscularis　thickness,　and　mucosal　thickness　were　statistically　significant　parameters　(P＜0.05).　For　the　OCT　images,　only　the　length　of　the　basilar　part　and　submucosal　height　+　muscularis　thickness　were　statistically　significant　parameters　between　the　acute　colitis　mice　and　control-group　mice　(P＜0.05).　The　length　of　the　basilar　part　and　submucosal　height　+　muscularis　thickness　were　statistically　significant　between　chronic　colitis　mice　and　control-group　mice　(P＜0.05).　In　the　comparisons　between　acute　colitis　mice　and　those　with　chronic　colitis,　only　submucosal　height　+　muscularis　thickness　was　a　statistically　significant　parameter　(P＜0.05).　Conclusions:　Certain　intestinal　wall　parameters　in　OCT　can　be　used　to　make　a　differential　diagnosis　between　acute　and　chronic　colitis　possible.　This　study　contributes　to　constructing　a　potential　diagnostic　system　for　evaluating　colorectal　inflammation　using　OCT.　©　2022　Quantitative　Imaging　in　Medicine　and　Surgery.　All　rights　reserved.