Objective To investigate the relationship between serum glucose-6-phosphate isomerase (GPI) and disease activity in patients with rheumatoid arthritis (RA) and its role in bone erosion. Methods One hundred and five patients with RA, who were admitted to the Department of Rheumatology, Fenyang Hospital of Shanxi Province from August 2019 to February 2021, were divided into GPI positive group and GPI negative group according to the titer of serum GPI determined by enzyme-linked immunosorbent assay (ELISA). The two groups were compared in the clinical data and laboratory indexes which included swollen joint count(SJC), tender joint count(TJC), anti-cyclic citrullinated peptide (CCP) antibody, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), the 28-joint disease activity score (DAS28)was calculated , conventional radiographs of bilateral hands and bone mineral density was performed, and the Sharp score was also calculated. All patients were given standard treatment and followed up regularly, disease activity was assessed after 3, 6, 9 and 12 months' treatment, DAS28 scores were recorded, and radiological indexes were reviewed after one year's treatment. Results SJC[5.00(4.00, 6.00)],TJC[6.00(5.00, 8.75)],ESR[(58.70±23.40) mm/h)],CRP[21.82(13.55, 31.90) mg/L] and DAS28 score(5.44±0.69) in GPI positive group were higher than GPI negative group[4.00(3.00, 5.00)、5.00(5.00, 7.00)、(48.72±19.87) mm/h、14.37(6.49, 26.56) mg/L、(5.05±0.50)], there were statistically differences(P<0.05). Serum GPI level was positively correlated with SJC(r=0.317, P=0.046),TJC(r=0.389, P=0.013),ESR(r=0.331, P=0.037),CRP(r=0.324, P=0.042) and DAS28 score(r=0.404, P=0.010), DAS28 score in GPI positive group was higher than GPI negative group after 3 months' treatment[(3.27±0.68) vs. (3.00±0.58)], and the difference was statistically significant(P<0.05). The difference was not statistically significant in Sharp score and bone mineral density between the two groups before and after treatment. Conclusions GPI can be used as an indicator of RA disease activity, which has nothing to do with bone erosion, but may play a role in evaluating prognosis.