The　mesothelial-mesenchymal　transition　(MMT)　of　peritoneal　mesothelial　cells　is　a　critical　factor　contributing　to　the　progression　of　peritoneal　fibrosis.　This　study　aimed　to　explore　the　effect　of　cGAS-STING　signaling　pathway　on　the　MMT　process　in　peritoneal　mesothelial　cells.　The　expressions　of　cGAS,　STING,　alpha-SMA,　and　Vimentin　in　HMrSV5　cells　treated　with　high　glucose　were　analyzed　using　WB.　Subsequently,　si-cGAS　and　the　cGAS　inhibitor　RU.521　were　employed　to　intervene　in　HMrSV5　cells.　qPCR　was　utilized　to　evaluate　the　expression　levels　of　genes　involved　in　the　cGAS-STING　signaling　pathway　(cGAS,　STING,　IRF3,　TBK1)　and　MMT-related　genes　(E-cadherin,　Vimentin,　alpha-SMA,　TGF-beta　1).　The　protein　expressions　of　the　cGAS-STING　signaling　pathway　and　MMT-related　proteins　were　detected　by　WB.　The　invasive　capacity　of　cells　in　each　cell　was　assessed　using　a　Transwell　assay,　and　the　levels　of　pro-inflammatory　cytokines　(IL-6,　TNF-alpha)　in　the　supernatants　of　each　cell　were　measured　by　ELISA.　In　the　present　study,　we　found　that　the　expressions　of　cGAS,　p-STING/STING,　p-IRF3/IRF3,　and　p-TBK1/TBK1　proteins　were　significantly　upregulated　in　HG-treated　HMrSV5　cells.　Furthermore,　the　activation　of　the　cGAS-STING　signaling　pathway　could　be　effectively　suppressed　in　HMrSV5　cells　transfected　with　si-cGAS　or　treated　with　RU.521.　Additionally,　treatment　with　si-cGAS　or　RU.521　not　only　attenuated　the　invasive　capacity　of　HMrSV5　cells　but　also　decreased　the　levels　of　pro-inflammatory　cytokines　and　inhibited　the　expression　of　MMT-related　markers.　Suppression　of　the　cGAS-STING　signaling　pathway　mitigates　HG-induced　MMT　in　the　human　peritoneal　mesothelial　cell　line　HMrSV5.