In this paper， the effects of two high F oligopeptides， M2 and M3， which were prepared from tuna minced meat and purified， on the intestinal flora structure of mice were investigated. By intragastric solutions of M2 and M3， intestinal contents of mice were collected， and DNA was extracted for 16s rRNA sequencing. Species composition and abundance distribution of intestinal flora of mice were analyzed using Anosim， OTUvenn， OUT PCA， PCoA and LDA EffectSize. The results showed that the intestinal microflora structure of the mice in the three groups was different， but the microflora of the two oligopeptides groups were less different， and the composition of the microflora of the blank group was significantly different. The total amount of bacteroidetes and firmicutes in the two oligopeptides groups was 90.17% and 91.73%， respectively， both higher than 88.20% in the blank group. At the level of the two oligopeptides， the dominant bacteria were spirillaceae， riken and prevotella， while the blank group was plasmodiaceae. The dominant characteristic bacteria of the M2 oligopeptide group were the invisible corpuscular family， the dominant characteristic bacteria of the M3 oligopeptide group were the rikenellaceae， mycobacterium and the methylobacteriaceae， and the dominant characteristic bacteria of the blank group were the purple single cells and moraxaceae. The results indicated that high F value oligopeptides M2 and M3 could regulate the structure of intestinal flora of mice， promote the proliferation of beneficial bacteria， and thus improve the intestinal microecology of inflammatory mice， laying a foundation for the subsequent study on the anti-inflammation activity of the high F oligopeptin M3.