Objective: To investigate the changes in gut microbiota structure after Tangnaikang(TNK) intervention in Zucker diabetic fatty rats (ZDF

fa/fa) and ZDF (fa/+) with spontaneous type 2 diabetes mellitus. Method: Six male ZDF (fa/+) rats were set as normal control group

and eighteen male (fa/fa) ZDF rats (mean value of random blood glucose in different days ≥ 11.1 mmol·L-1) were set as T2DM model group and divided into model group (normal saline

10 mL·kg-1)

TNK high-dose (TH

3.24 g·kg-1) and TNK low-dose (TL

0.81 g·kg-1) groups depending on their body weight and random blood glucose (RBG)

n=6 in each group. After 6 weeks of drug administration

blood was taken from abdominal aorta to detect their fasting plasma glucose (FPG) and fasting serum insulin (FINS)

fecal samples were collected from the rats to detect microbiota by reverse transcription-polymerase chain reaction (RT-PCR)

and amplicon pyrose quencing was taken to analyze the changes of microbiota in 16S rRNA V4 region. Result: Both TH group and TL group had significant differences in FPG and FINS as compared with model group (P<0.01). There were significant differences in flora diversity and structure composition between various groups. At the family level and below

the abundance of Lactobacillaceae was increased in model group as compared with control group (P<0.05); while as compared with model group

the abundance of Lactobacillaceae was decreased in TH group and TL group without statistical difference

and the abundance of Prevotella was significantly increased (P<0.01)

in addition

Prevotella had a positive correlation with FINS in ZDF rats. Conclusion: The ZDF(fa/fa) and their lean llittermates ZDF(fa/+) had significant differences in microbial composition

and TNK may improve the blood glucose by affecting the abundance of Prevotella and the Lactobacillaceae in intestine of the ZDF rats.