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Objective: The aim of this review was to identify the possible mechanisms behind cupping therapy by employing an evidence-based approach,and to explore its possible regional and systemic effects in the human body.Methods: We searched six electronic databases and four online trial registries for articles published up to January 1,2020.Clinical studies on the mechanisms of retained cupping,flashing cupping,moving cupping,and vacuum cupping were considered for this review.The methodological qualities of controlled studies were assessed using the National Institute for Clinical Excellence methodology checklist,the Newcastle-Ottawa Scale,and the Cochrane risk of bias tool.Characteristic statistical description and qualitative summary of results were used for data analysis.Results: Thirty-eight studies(37 full texts and one abstract)were included in this study.Due to the clinical heterogeneity among the studies,we could not conduct a meta-analysis.The results showed that the key factors that contribute to the efficacy of cupping therapy are negative pressure and temperature.Cupping therapy mainly causes local and systemic changes in hemodynamics,immune regulation,metabolism,and pain relief.Conclusion: We identified negative pressure as the key element behind cupping therapy.Cupping therapy may cause redistribution of oxygen at the cupping site and in neighboring tissues,thereby inducing a therapeutic effect by increasing regional blood flow.It may also induce metabolic change,immunomodulation,and neuromodulation.However,additional rigorous clinical research needs to be conducted to further clarify the mechanism behind cupping therapy.