[Objective] To investigate the difference of gut microbiota between knee osteoarthritis (KOA) and normal control in rabbits. [Methods] A total of 20 Japanese white rabbits were randomly divided into 2 groups, of them, 12 animals were injected 2% papain solution intraarticularly to prepare KOA model, while the other 8 rabbits were injected normal saline intraarticularly as normal control. Fecal sam- ples were collected and detected by 16S rRNA gene targeted sequencing technology to analyze the diversity and distribution of gut microbio- ta in their feces. [Results] The KOA group had a total of 20 188 species (ASV/OTU) , while the control group was of 14 029 species (ASV/ OTU) . The fecal flora in KOA group was significantly more abundant than that in the control group in levels of phylum and genus (P< 0.05) , but there were no statistical significant differences in the levels of class, order, family and specie between the two groups (P>0.05) . The KOA group had the greatest number of firmicutes and bacteroides at phylum level, and ruminococcus and spironella flutter at genus lev- el, with an obvious marker species of proteus. The gut microbiota was closely related to metabolic pathways, especially carbohydrate metab- olism, amino acid metabolism, cofactor and vitamin metabolism. [Conclusion] There are some differences in gut microbiota between KOA group and control group, and proteus is the marker species.