Microorganisms are a vital part of lake ecosystems, which drive nutrient cycling and energy conversion in aquatic ecosystems, and on the other hand are highly sensitive to changes of environmental factors, being oftentimes used as indicator organisms for the evolution of lake ecosystems. As for Chaohu Lake, it is of great significance to study the differences in microbial community structure at different lake inlets and their relationship with environmental factors. In this study, the high-throughput sequencing technology based on 16S rRNA gene was used to analyze the structure of microbial communities in different inlets of the Lake, and a covariate network of dominant microorganisms was constructed by adopting the principle of stochastic matrix to investigate the differences in inter-species relationships among microorganisms in different inlets, and then MRM and Mantel Test analyses were used to reveal the driving factors of the microbial communities and their response strategies to the environmental changes. The analysis by methods of MRM (multiple linear regression) and Mantel Test revealed the driving factors of different microbial communities in the lake inlets and their responsive strategies to cope with the environmental changes. Findings of the study showed that microbial communities in inlets of into-lake rivers of the Nanfei River and Paihe River were of a rather good similarity, and the microbial community structure of the into-lake river Hangbu River inlet was obviously different, and the common dominant microorganisms of these three inlets were related to nitrification and denitrification, and the microorganisms of the three inlets are all related to the function of nitrification and denitrification; the dominant microorganisms endemic in the Nanfei River inlet included Flavobacteriaceae, Steroidobacteraceae, Sphingomonadaceae and Sutterellaceae, the unique dominant microorganisms in the inlet of the Paihe River was Rhodanobacteraceae and Hydrogenophilaceae, and the unique dominant microorganisms in the Hangbu River inlet were Vicinamibacteraceae and Methylomonadaceae. The results of the microbial co-linear network suggested that the Nanfei River inlet had the highest symbiotic microbial network, and the key species in the microbial network of different inlets were related to the nitro - gen transformation function; the MRM analysis showed that there existed differences in the driving factors of microbial community structure in different lake inlets; the key driving factors in the inlet of the Nanfei River were water temperature and the content of NO3--N, the key driving factor in the inlet of the Paihe River was the content of NH4+-N, and the key driving factors in the inlet of the Hangbu River were temperature, TP, and COD content; and the Mantel Test analysis indicated that all of the microorganisms in different lakes were dominant microorganisms with large differences in relative abundance, which were affected by the driving factors. Mantel Test analysis showed that the microorganisms affected by the driving factors in different lake inlets were dominant microorganisms with greater differences in relative abundance. In conclusion, the environmental differences in the lake inlets resulted in certain differences in terms of the composition and structure of microbial communities; the microbial symbiosis was more distinct in the inlets with higher nutrient levels; and the environment naturally had a selective effect on the microorganisms to maintain the stability of the ecological environment. [ABSTRACT FROM AUTHOR]