Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 17 1 2025 02 05 59 68 EN Reyhaneh Shekari Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Gholamreza Zarrini Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Vahid Siahpoush Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz, Iran Farzam Sheikhzadeh Hesari Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran 2023 10 22 2025 01 06 Background and Objectives: Antibiotic resistance in microorganisms is a significant global health concern. Cold atmospheric plasma is an innovative and promising method for inactivating bacteria. This study aimed to evaluate the effects of cold plasma on Pseudomonas aeruginosa in a mouse wound infection model. Materials and Methods: The disk diffusion method was used to perform antibiograms after isolating the bacteria. A multidrug-resistant strain was then selected. The bactericidal activity of cold helium plasma was investigated in vitro. The optimal cold plasma conditions were determined in the laboratory, with a flow of 3 liters per minute and a power of 1.1 watts. These conditions were later used for in vivo evaluations. Results: In a laboratory study, helium gas plasma treatment for 8 minutes reduced P. aeruginosa by 2.5 logs. In the in vivo study, plasma reduced the wound's microbial load in mice by 1.9 log. The antibiotic treatment group had a 1.2 log reduction. Both plasma and antibiotic therapies had similar effects on microbial inactivation. Conclusion: The overall evaluation of wound healing time and pathological features showed that plasma was generally better than antibiotic treatment. Plasma can inactivate P. aeruginosa in wounds and accelerate wound healing. https://ijm.tums.ac.ir/index.php/ijm/article/view/4453 https://ijm.tums.ac.ir/index.php/ijm/article/download/4453/1742