Objective To investigate the effects of lncRNA-H19 on fibroblast-like synovial cells(FLS) and collagen induced arthritis (CIA) mice. Methods With FLS isolated and cultured from patients with rheumatoid arthritis (RA), adenovirus, lentivirus and siRNA were used to up-regulate and down-regulate the expression of H19 in RA FLS. BrdU, TranswellTM assay and cell scratch assay were employed to evaluate the proliferation, invasion and migration of RA FLS, respectively. Mice with CIA were locally injected with LV-sh-H19. The progression of CIA was observed by paw thickness, clinical arthritic index, and histologic analysis. Results The expression of H19 was closely associated with the proliferation, invasion and migration of FLS cells and knockdown of H19 significantly ameliorated the progression of CIA in mice. Conclusion H19 is involved in synovial inflammation and progression in CIA mice by promoting the activation of FLS.