Geniposide (GE), an iridoid glycoside compound purified from Gardenia jasminoides Ellis, has antiinflammatory and other pharmacological effects, but its mechanism of actions on rheumatoid arthritis (RA) have not been clarified. The purpose of this article was to investigate the pharmacological effects of GE on collagen-induced arthritis (CIA) rats and its feasible mechanisms. Collagen-induced arthritis was induced by injection of chicken type II collagen emulsion. The rats were orally administered with GE (33, 66, and 132 mg/kg) from days 14 to 30 after immunization. The histological examination showed that GE could attenuate histopathologic changes of mesenteric lymph node (MLN) in CIA rats. Geniposide inhibited the production of Interleukin 6 (IL-6) and IL-17, while promoting the production of IL-4 and transforming growth factor-beta 1 in MLN lymphocytes (MLNLs). Moreover, the proliferation capability of MLNLs was increased after the administration of GE. In addition, the treatment with GE in vivo decreased the expressions of P-Raf, P-MEK, and P-Erk1/2 in MLNLs. These results may highlight the antiinflammatory effects and possible mechanisms of GE in MLNLs of RA. Copyright (c) 2017 John Wiley & Sons, Ltd.