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Objective: To study the effect of Yangqixue Qufengshi Recipe (养气血祛风湿方, YQXQFS)on rheumatoid arthritis (RA) model mice under different genetic backgrounds. Methods: Collagen Induced Arthritis (CIA) were established on HLA-DR4 transgenic (TG) mice and non-transgenic (NTG) mice, which partly were raised with YQXQFS, and the onset day of CIA, the level of type Ⅱ collagen (C Ⅱ )-reactive antibodies and the pathological scores of CIA were assessed. Results: Under HLA-DR4 TG background (compared with NTG mice), the earlier onset day of CIA ( 11.22 ± 3.35 days vs 16.56 ± 4.75 days, P＜0.05)and higher level of C Ⅱ -reactive antibodies (0. 2274 ± 0. 1390 μg/ml vs 0. 1101 ± 0. 0560 μg/ml, P＜0.05)were observed, but the pathological scores of CIA remained unchange. YQXQFS could not influence the onset day of CIA and the level of C Ⅱ-reactive antibodies, but had a certain effect on the total pathological scores (6.56 ± 3.43 scores vs 11.11 ± 5.64 scores) and bone erosion (0.22 ± 0.44 scores vs 1.67 ± 1.50 scores)of CIA on NTG mice (P＜0.05), NTG YQXQFS group compared with NTG experimental group. Conclusion:YQXQFS had a certain effect on RA model, but had no significant effect on HLA-DR4 related CIA.