Objective To explore how leptin affects RA,especially those with joint erosion.Methods The study recruited 48 consecutive patients with RA (14 patients with knee joint effusion) and 23 age and sex matched healthy people.RA patients were grouped into low and moderate activity group [2.6＜28-joint disease activity score (DAS28) ≤5.1,n =5] and high activity group (DAS28 ＞5.1,n =43) according DAS28-ESR;Meanwhile,they were grouped into bone erosive group (n=20) and non-erosive group (n=28) according to X-ray of both hands.Demographic data of RA patients were recorded.ELISA was applied to assess leptin and a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS4) in serum and synovial fluid of RA group.Sharp/van der Heijde scores were used to assess bone erosion and joint space narrowing.Leptin and ADAMTS4 from serum and synovial fluid were compared between different groups using t test,Rank sum test,Chi-square test and Analysis of Variance,and we did Pearson and Spearman's Corre-lation analyses between these values and clinical features,lab indicators and radiological scores.Moreover,we did single factor and logistic regression analyses,which facilitated screening risk factors of joint destruction.Results Serum leptin in RA group was significantly higher than that of the control group [8.06(6.24) ng/ml vs 4.62(7.13),Z=-2.113,P=0.035],and leptin was positively correlated with Shar/van der Heijde score (r=0.347,P=0.016).Serum leptin in erosive RA patients was higher than that of the non-erosive patients (Z=-2.070,P=0.038),and there was a positive correlation between leptin and ADAMTS4 only in synovial fluid of RA patients with erosion (r=0.900,P=0.037).It was found in logistic regression results that RA patients with more tender joint counts and elevated leptin were more likely to develop bone erosion [OR=1.229,95％CI (1.007,1.500),P=0.043;OR=1.159,95％CI (1.015,1.324),P=0.030].Conclusion Leptin participates RA joint destruction probably by modulating expression of ADAMTS4.Leptin and tender joint count are independent risk factors for RA with joint destruction.