The immunomodulatory potential of certain bacterial strains suggests that they could be beneficial in the treatment of rheumatoid arthritis (RA). In this study, we investigated the effects of Bifidobacterium longum subsp. infantis B6MNI on the progression of collagen-induced arthritis (CIA) in rats as well as its influence on the gut microbiota and fecal metabolites. Forty-eight female Wistar rats were divided into six groups that included a B6MNI group with CIA and intragastrically administered B. longum subsp. infantis B6MNI (10 9 CFU/day/rat), a control group (CON), and a CIA group, both of which were intracardiacally administered the same volume of saline. Rats were sacrificed after short-term (ST, 4 weeks) or long-term (LT, 6 weeks) administration. The results indicate that B. longum subsp. infantis B6MNI can modulate the gut microbiota and fecal metabolites, including 5-hydroxyindole-3-acetic acid (5-HIAA), which in turn impacts the expression of Pim-1 and immune cell differentiation, then through the JAK-STAT3 pathway affects joint inflammation, regulates osteoclast differentiation factors, and delays the progression of RA. Our results also suggest that B. longum subsp. infantis B6MNI is most efficacious for the early or middle stages of RA.