It has been suggested that IL-31/IL-31R signaling is a negative regulatory pathway that specifically limits Th2-dependent cytokine production. Given the fact that rheumatoid arthritis is a Th1/Th17-dependent autoimmune diseases, in the present study the sera and synovial fluid levels of IL-31 was compared between 44 patients with rheumatoid arthritis and 44 sex and aged matched osteoarthritic patients as controls. The levels of IL-31 were measured by commercial ELISA kits. Mean of IL-31 levels in the sera and synovial fluid of RA patients were 35.58±58.26 pg/ml and 16.03±26.71 pg/ml, respectively. While no statistical difference was detected in IL-31 sera levels between patients and OA controls (14.73±9.02 pg/ml, p=0.4), the levels of IL-31 in the synovial fluids of patients were significantly higher than controls (0.67±4.72 pg/ml, p<0.0001). However, no significant correlation was detected between the sera or synovial levels of IL-31 in RA patients and CRP levels or ESR. Interestingly, a significant positive correlation was also detected between the number of involved joints and sera levels of IL-31 (p=0.03). In addition, after categorization of patients according to joints deformity, a significant higher concentration of IL-31 was detected in the sera or synovial fluid of patients with joint deformity (40.21±63.07 pg/ml and 18.27±28.43 pg/ml, respectively) compared with those in patients without deformity (14.72±18.75 pg/ml and 5.96±14.19 pg/ml, respectively; p=0.04 and p=0.01, respectively). In conclusion IL-31 can be considered as a new pro-inflammatory cytokine in the pathogenesis of RA and might be considered as a new target for biologic therapy of RA.