To explore the effect of Baihe Dihuang Decoction on the behavior and intestinal flora of depressed rats.Methods:The rat model of depression was prepared by solitary feeding and chronic unpredictable mild stress stimulation.After administration of Baihe Dihuang Decoction，the pharmacodynamics were evaluated by sugar water preference test and open field test，and the colonic pathology of rats was examined.Meanwhile，rat feces were collected，and 16S rRNA high-throughput sequencing technology was used to analyze the diversity of rat intestinal flora and predict its function.Results:Compared to the normal group，the weight of rats in the model group decreased significantly.After administration，the weight of rats in each dose group had a tendency to increase.The results of sugar water preference experiment showed that the sugar water preference of rats in the model group was significantly weakened compared to the normal group(P<0.01).After administration，the preference for sugar water in all dose groups increased，and the difference between medium dose group and low dose group was statistically significant(P<0.01).In an open field experiment，compared to the normal group，the autonomic activity of rats in the model group significantly decreased(P<0.01).After administration，the autonomous activity of rats in all dose groups had a trend of enhancement，and the difference between the low-dose group and the model group was statistically significant(P<0.05).The pathological results showed that the colonic mucosa of the model group was destroyed，and the colonic mucosa of each administration group recovered to different degrees after receiving Baihe Dihuang Decoction.In terms of bacterial diversity，after treatment with Baihe Dihuang Decoction，the abundance of Firmicutes increased，and the abundance of Bacteroidota，Verrucomicrobia，Proteobacteria and Cyanobacteria decreased.The changes of Proteobacteria and Cyanobacteria were statistically significant(P<0.05).At the genus level，the abundances of genera such as norank_f__Muribaculaceae，Ruminococcus and Faecalibacterium decreased，and the abundance of genera such as Lactobacillus，Rombutzia，Turicibacter and Bacillus increased.The changes in norank_f__Muribaculaceae，Rombutzia，Turicibacter，norank_f__Eubacterium_coprostanoligenes_group，Prevotellaceae_UCG-001 and Prevotellaceae_UCG-001 were statistically significant(P<0.05).KEGG function prediction showed that the function of different flora was related to amino acid metabolism，energy metabolism，nervous system and neurodegenerative diseases.Conclusion:Baihe Dihuang Decoction can improve the depression-like behavior of depressed rats by regulating the intestinal flora of depressed rats.