Abstract： Objective To evaluate the effects of andrographolide on insulin resistance,dysbiosis and Notch/zinc finger protein transcription factor 1(Snail1)signaling pathway in diabetic rats.Methods A total of 70 male Wistar rats with SPF grade were selected,and 30 of them were selected for andrographolide LD50 test.After determining the lethal dose,50 mg/kg was selected for administration and observation,the remaining 40 rats,10 were used as the NC group,30 were established as the diabetes model,and a total of 28 rats were successfully modeled,which were divided into T2DM group(n=9),Metformin treatment group(Met,n=9),and andrographolide administration group(And,n=10).The NC group and T2DM group were not treated.The changes were evaluated after 14 days of intervention.Results Compared with NC group,HOMA-IR,the abundance levels of Bacteroidetes,Firmicute,mRNA and protein expression levels of Notch and Snail1,and positive expression rates were increased(P<0.05),while the abundance levels of Lactobacillus and Bifidobacterium were decreased in T2DM,Met and And group(P<0.05).Compared with T2DM group,HOMA-IR,the abundance levels of Bacteroidetes,Firmicute,mRNA and protein expression levels of Notch and Snail1,and positive expression rates were decreased,while the abundance levels of Lactobacillus and bifidobacterium were increased in Met and And group(P<0.05).Conclusions After andrographolide intervention,insulin resistance was alleviated,microbiota imbalance was improved,and Notch/Snail1 signaling pathway was suppressed in diabetic rats.