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As a representative technology in plasma medicine, cold atmospheric plasma (CAP) has beneficial outcomes in surface disinfection, wound repair, tissue regeneration, solid tumor therapy. Impact on immune response and inflammatory conditions was also observed in the process of CAP treatment. Relevant literatures were collected to assess efficacy and summarize possible mechanisms of the innovation. CAP mediates alteration in local immune microenvironment mainly through two ways. One is to down-regulate the expression level of several cytokines, impeding further conduction of immune or inflammatory signals. Intervening the functional phenotype of cells through different degree of oxidative stress is the other approach to manage the immune-mediated inflammatory disorders. A series of preclinical and clinical studies confirmed the therapeutic effect and side effects free of CAP. Moreover, several suggestions proposed in this manuscript might help to find directions for future investigation.