To elucidate the clinical relevance of P-gp expression and function to MDR in patients with rheumatoid arthritis (RA). Samples were divided into 4 groups: the control, incipient RA, effectively cured RA, refractory RA group. First, P-gp expression was determined by FCM, P-gp function by Rh-123 accumulation assay, mRNA expression of P-gp in PBMC by RT-PCR and TNF-alpha level in serum by ELISA. Correlation analysis between them was performed. Then, interference by TNF-alpha on PBMC from the 4 groups for 2, 6, 12 and 24 h was performed, respectively. P-gp expression and function was determined by FCM and Rh-123 accumulation assay, respectively. P-gp expression and function, TNF-alpha mRNA expression and serum TNF-alpha level in the control were all much lower than that in RA groups. In RA groups, the values in refractory RA group were much higher than the other groups, and values in effectively cured RA group were the lowest. P-gp expression had a positive correlation with mRNA expression of TNF-alpha, serum TNF-alpha level and DAS28 score. However, the results on Rh-123 fluorescence intensity were opposite. After interference by TNF-alpha, P-gp expression and function in refractory RA group were sensitive to the stimulation of TNF-alpha with same concentration in RA groups. TNF-alpha can up-regulate PBMC P-gp expression and function in patients with RA, mediate the MDR of RA and participate in the formation of RRA.