Abstract： Objective:To investigate the clinical efficacy of Tetrandrine combined with Cyclophosphamide in the treatment of rheumatoid arthritis (RA) complicated with interstitial lung disease (ILD) .Methods:A total of 110 patients with RA complicated with ILD admitted to Yancheng First Municipal People’s Hospital were randomly divided into Cyclophosphamide group and combination therapy group ( n=55 each) . The Cyclophosphamide group was given Cyclophosphamide pulse therapy. The combination therapy group was given Tetrandrine and Cyclophosphamide. At baseline, bronchoscopic lung biopsy, alveolar lavage, high-resolution CT (HRCT) scoring, clinical radiological and physiological scoring were performed. At 6 months after the treatment, all patients were followed up, re-reviewed, and compared for clinical radiological and physiological scores between the two groups. Results:After the treatment, the clinical radiological and physiological scores, pulmonary function, dyspnea score, and arterial partial pressure of oxygen in the combination therapy group were improved more significantly compared with the Cyclophosphamide group (all P<0.05) . The response rate in the Cyclophosphamide group and combination therapy group was 36% (18/50) vs 69% (35/51) ( P<0.05) . In the alveolar lavage fluid, the neutrophil count in the combination therapy group was much more lowered than that in the Cyclophosphamide group ( P<0.05) . During the treatment, there were no Tetrandrine-related adverse reactions in the combination therapy group. The adverse reactions were mainly related to Cyclophosphamide, especially respiratory infections. The incidence of adverse reactions in the combination therapy group was lower than that in the Cyclophosphamide group [5.5% (3/55) vs 18.2% (10/55) ] ( P<0.05) . Conclusion:Tetrandrine combined with Cyclophosphamide pulse therapy is more effective than cyclophosphamide alone in the treatment of RA and ILD, with good medication safety.