The pathogenesis of diabetes and diabetic kidney disease (DKD) is closely related to the imbalance of gut microbiota. We aimed to explore whether exogenous Akkermansia muciniphila (A. muciniphila) supplementation affected the progression of DKD.The feces from normal subjects, diabetic patients without kidney diseases, and patients with DKD were collected, and the changes in microbial communities were analyzed. A rodent db/db DKD model was also constructed to investigate whether the abundance of A. muciniphila would be altered in response to renal function decline. The measurement of inflammatory cytokines in peripheral blood, fecal short-chain fatty acids (SCFAs), renal histopathology, and Western blot analysis were carried out to further evaluate the effects of A. muciniphila.The relative abundance of A. muciniphila was found to be lower in the feces of DKD patients and also in the intestine of DKD mice. After exogenous supplementation of A. muciniphila, the levels of urinary protein, blood urea nitrogen, and creatinine decreased in DKD mice, as well as uremic toxins, trimethylamine-N-oxide (TMAO), p-cresol sulfonate, and indole sulfonate. A. muciniphila supplementation also increased the SCFAs gut production. The supplementation also protected the integrity of the intestinal mucosa by increasing MUC2, occludin, and zona occludens 1 (ZO-1) protein expression in the intestinal wall.Exogenous supplementation of A. muciniphila improved the imbalance of gut microbiota, reduced systemic inflammation, decreased uremic toxins, and protected the integrity of the intestinal mucosa, thus delaying DKD progression.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.