Rheumatoid arthritis (RA) is a chronic inflammatory disorder that is caused by the immune system that mistakenly attacks the joints. Collagen-induced arthritis (CIA) is widely accepted as an animal model for RA and has contributed to the understanding of the pathogenesis and the development of therapy. Here, we found a substance X that diminished clinical conditions of CIA. The substance X was repeatedly administered before and after induction of CIA in DBA/1J mice and we monitored the mice to evaluate the clinical score and the incidence. We assessed four histological parameters, including leukocyte infiltration, pannus formation, cartilage damage, and bone destruction. In addition, we determined the concentration of pro-inflammatory cytokines in serum. The arthritic scores of DBA/1J mice that were injected by the substance X were lower than those of PBS-treated DBA/1J mice. Histological evaluation of the four parameters showed significant reductions of histological severities in DAB/1J mice injected by the substance X, compared to those of PBS-treated mice. Serum concentration of two pro-inflammatory cytokines was significantly decreased in DBA/1J mice injected by the substance X. These data suggests that the substance X reduces inflammation caused by immune responses and ameliorates the severity of arthritic score and bone damage. The substance may be a new potential medicine for the treatment of RA.