Abstract: 【Objective】 This study aimed to perform isolation， culture， and functional analysis of sheep-derived Akkermansia massiliensis， so as to provide a theoretical basis for the control of intestinal inflammatory diseases of sheep and the probiotic potential of sheep-derived Akkermansia massiliensis in intestinal health.【Method】 Fresh sheep feces were collected to isolate and identify an Akkermansia massiliensis strain under the anaerobic condition at 37 °C. The genomic characteristics and potential functions were analyzed by whole-genome sequencing. A mouse model of colitis induced by sodium dextran sulfate （DSS） was constructed， and the inhibitory effects of Akkermansia massiliensis on intestinal inflammation and its regulatory role in the intestinal microbiota composition were evaluated via gavage intervention.【Result】 Ms2526 strain showed a 100% genome integrity， a contamination rate of 0.12%， a coding density of 0.874， a genome length of 3112518 bp， a GC content of 58%， and a total of 2622 genes. Ms2526 was most closely related to the EB-AMDK-40 of Akkermansia massiliensis， clustering together with a 99% self-spreading support rate， and differed in branch length from other Akkermansia massiliensis strains such as Akk2000. The Ms2526 genome contained coding genes highly homologous to Amuc_1100 and P9 proteins. Coding genes of Ms2526 genome were mostly enriched in metabolic pathways， including signaling pathways related to carbohydrate metabolism， cofactor and vitamin metabolism， biosynthesis of other secondary metabolites， and terpenes and polyketides metabolism. Five genes were enriched in immune system signaling pathways among the organismal system categories. The Ms2526 genome contained 157 genes annotated to six major classes of carbo-hydrate active enzymes， with higher numbers of genes annotated to glycosyltransferases and glycoside hydrolases. The Ms2526 genome contained one macrolide antibiotic resistance gene， erm（B）. The Ms2526 could alleviate DSS-induced colitis in mice， improve the integrity of colonic tissues and mucosal structure， and increase the abundance of intestinal microbiota species.【Conclusion】 The Ms2526 genome of sheep-derived Akkermansia massiliensis has genetic basis related to carbohydrate metabolism， immune homeostasis regulation， and mucosal repair. The Ms2526 strain effectively alleviates DSS-induced colitis in mice， and its effect is closely related to enhancing intestinal barrier integrity， regulating systemic inflammation， and restoring the richness of intestinal microbiota. The Ms2526 strain demonstrates good probiotic potential in regulating intestinal health.