OBJECTIVE： To observe the clinical efficacy and safety of leflunomide combined with prednisone in the treatment of polymyositis. METHODS： Totally 98 polymyositis patients in our hospital were divided into observation group and control group by random number table， 49 cases in each group. Control group received Prednisone tablet with initial dose of 60-100 mg/d， tid， then gradually reduced to maintaining dose of 10 mg/d， tid， based on patients’ improvement of creatine kinase （CK） and clinical symptoms. Observation group was additionally given Leflunomide tablet 10 mg， bid， based on the control group. They all treated for 120 d. Clinical efficacy， muscle strength evaluation， muscle enzymes [including CK， lactate dehydrogenase （LDH）， aspartate aminotransferase （AST）， creatine phosphokinase （CPK）， alanine aminotransferase （ALT）] and serum inflammatory factors （including IL-2， IL-8， IL-12， TNF-α， hs-CRP） before and after treatment in 2 groups were observed， the incidence of adverse reactions in 2 groups was recorded. RESULTS： After treatment， the total effective rate （87.8％ vs. 75.5％） and muscle strength achieving grade 3 （81.6％ vs. 55.1％） in observation group were significantly higher than control group， and the total adverse reaction rate （12.2％ vs. 22.4％） was lower than control， with statistically significances （P＜0.05）. After treatment， the muscle enzymes and serum inflammatory factor levels in groups were significantly lower than before， and observation group was lower than control group， with statistically significances （P＜0.05）. CONCLUSIONS： Leflunomide combined with prednisone shows good efficacy in the treatment of polymyositis， it can significantly improve the muscle strength， muscle enzymes and serum inflammatory factor levels， and dose not increase the incidence of adverse reactions， with good safety.