Objective To review the mechanism of cold atmospheric plasma (CAP) in the treatment of chronic skin ulcer, providing a new idea for ulcer therapy. Methods The literature about CAP in the treatment of chronic skin ulcers in recent years was extensively screened and reviewed. The treatment principle, active ingredients, and mechanism were summarized. Results CAP is partial ionized gas discharged by plasma generator in high frequency under high voltage. It contains electrons, positive and negative ions, reactive oxygen species, reactive nitrogen species, and ultraviolet rays. In vitro and animal experiments show that the active ingredients contained in CAP can inactive microorganisms, against biofilm, regulate immune-mediated inflammatory, promoting blood flow, stimulate tissue regeneration and epithelial formation in the course of wounds healing. Conclusion CAP play a role in different stages of chronic skin ulcer healing, with good efficacy and safety, and broad clinical application prospects. But more studies are needed to explore the indications and dosages of CAP therapy.