Abstract: Abstract: Objective: Observing the dynamic changes of the intestinal mucosal morphous in self-healing diarrhea mice, providing a theoretical basis for researching the antidiarrheal drugs. Methods: The mouse diarrheal model was established by intraperitoneal injection of E.coli O101. The pathological changes of intestinal mucosal were observed by Light microscopy（LM）, scanning electron microscopy（SEM）and transmission electron microscope(TEM). Results: the treated mice show gloomy, yellow thin feces, there were sporadic bleeding points on duodenum. the intestinal wall became thinner. Through the LM, the intestine villi were broken, epithelial cells were swelled, some inflammatory cell were infiltrated in the intestinal submucosa.Under the SEM, intestinal villi and microvillus were swelled and appeared clutter, the number of goblet cells were increased. According to the observed of TEM，mitochondrial of the epithelial cells were vacuolized, the cristae and membrane had disappeared. Rough endoplasmic reticulums were expansion. Goblet cells contain a large number of original particles stick. Conclusion: In the self-healing process of mice diarrhea induced by E. coli O101, the clinical symptoms, Gross Anatomy and Microscopic changes were basically conformity. The intestinal pathological changes were marked in 1-3d after diarrhea, the clinical symptoms were improved after 4d, the mice were healed after 6d.