Objective: To identify the differential proteins in the serum with anti-asthma activity of acupuncture to pinpoint the substance basis of anti-asthma activity of acupuncture by proteomics method. Methods: Two-dimensional electrophoresis of protein was employed to analyze the differential proteins in the serum with anti-asthma activity of acupuncture, and identify the differential proteins with mass spectrum technique. Results: In adrenaleetomy (ADX)-asthma acupuncture group and asthma acupuncture group, two-dimensional eleetrophoresis showed that there was an obvious fuscous point (MW=44.1kD, PI=5.1), which was 60S ribosomal protein L13, or hypothetical protein FLJ32191 analyzed by mass spectrum technique, different from other groups. In ADX-asthma acupuncture group, there were two obviously fuseous points (MW=39.8kD, PI=4.9 and MW=39.5kD, PI=5.0), which were zinc finger protein 208, and thyroid hormone receptor-associated protein analyzed by mass spectrum technique, and two special proteins (MW=17.3kD, PI〈4.5 and 16.9kD, PI〈4.5), which were Cyclophilin A and zinc finger protein 91 analyzed by mass spectrum technique, different from other groups. Conclusion: There are multi-target effects regulating the whole body in acupuncture treating asthma relating to immunoloregulation, gene expression, and protein svnthesization. The effects of acupuncture on the resnonse nroteins need further research.