Abstract: Microcystin-LR has been known to harm the health in both humans and animals. Recently there has been an increase in reports about gastrointestinal ailments resulting from the ingestion of MCLR. Some data also indicated that MCLR could accumulate in the intestinal tract and cause injuries. In this study, we intraperitoneally injected mice with MCLR for 28 days, and observed the pathophysiological and ultrastructural changes. We also examined the activities of intestinal mucosal brush border membrane enzymes. Severe injuries were found in villi, such as a decrease in villi number and the exfoliation of villi into gut cavity. The cells of lamina propria and submucosa showed swell and hyperemia. In the ultrathin sections, loss of density in the cytoplasm associated with swollen mitochondria as well as nuclei deformation was observed. The activities of intestinal disaccharidase (sucrase, maltase, lactase), alkaline phosphatase, and -glutamyl transferase decreased after the MCLR exposure. Based on these results, we reasoned that the digestion capacity of small intestine might be inhibited after subchronic exposure of MCLR, which led to malabsorption. Our study suggested new cellular mechanisms that explain gastrointestinal sickness, such as nausea, vomiting and diarrhea, induced by cyanobacterial toxins.