This work was designed to identify the effect of 5,7,3'-triacetyl hesperetin (TAHP) on rat adjuvant arthritis (AA) and further clarify the possible role of TAHP on modulating Janus kinase signal transducers and activators (JAK/STAT in this process. Freund's complete adjuvant was used to induce AA in rats. TAHP (33, 66, 132 mg/kg) was administered intragastrically. Secondary paw swelling, polyarthritis index, index of immune organs and histopathological assessment were used to evaluate the effects of TAHP on AA in rats. IL-6 in serum and in synovial tissues was examined with ELISA and RT-PCR. In addition, JAK2/STAT3 pathway-related key molecules mRNA expression in synovial tissues of AA rats were detected by RT-PCR and western blot respectively. It was found that TAHP (66, 132 mg/kg) could significantly inhibit secondary paw swelling, restore the index of immune organs and reduce polyarthritis index. Results of histopathological assessment showed that TAHP clearly ameliorated the pathological changes in AA rats. TAHP could downregulate the level of IL-6 in serum and in synovial tissues of AA rats. Besides, treatment with TAHP could decrease mRNA expressions of STAT3 and JAK2, as well as the ratio of p-JAK2/JAK2 protein and p-STAT3/STAT3 protein from synovial tissues. Thus, the paper demonstrated that TAHP had a therapeutic effect on AA in rats and the mechanisms were partly associated with modulating proinflammatory cytokine IL-6 production in serum and in synovial tissues and inhibiting excessive activation of JAK2/STAT3 signaling pathway which might play a crucial role in the pathogenesis of AA.