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Background and Aims The efficacy of a direct application of plasma needle to in vivo wound healing was experimentally studied in mice. This kind of plasma has achieved considerable success in blood coagulation and tissue restoration in mice. In the development of the present study, an argon plasma needle was chosen for coagulation purposes, whereas for healing purposes, a helium plasma needle was used. Methods Treatment was applied with a plasma needle produced by argon and helium to a wound induced in laboratory mice. Tissue regeneration was carried out by three argon plasma treatments with 0.5 SLPM flow for 1 min and three treatments of helium with 1.5 SLPM flow. Intervals between each treatment were 5 min and 60 min for argon and helium plasmas, respectively, thus completing a total treatment time of 180 min. Histological sections were performed to corroborate the internal bleeding and tissue regeneration. Results After three treatments with argon plasma, the blood produced in the wound was coagulated and protein material appeared. By means of treatment with helium plasma, an approach of the wound edges was produced until the conclusion thereof. These results were corroborated histologically. Conclusions This type of acceleration during the skin wound healing process can be attributed to the formation of reactive species such as NO, which were increased in the helium plasma needle with respect to the argon plasma needle.