The　short　lifetime　and　low　sensitivity　of　the　current　glucose　electrochemical　sensors　are　two　major　issues　for　implementing　continuous　real-time　monitoring　of　glucose　in　vivo.　Here　we　show　that　a　unique　microneedle-based　glucose　monitoring　skin　patch　(termed　here　MGMSP)　can　continuously　measure　glucose　in　real　time　in　live　animals　with　micromolar　sensitivity　and　over　14　days　of　service　life.　This　MGMSP　employs　a　glucose　oxidase　(GOD)　and　carbon　nanotube　(CNT)　modified　hollow　syringe　as　electrochemical　sensor　for　glucose　monitoring,　an　integrated　circuit　for　signal　processing　and　transmission,　and　the　real-time　glucose　levels　are　displayed　on　smartphone　via　Bluetooth.　The　designed　microneedle　device　protects　the　stability　of　the　sensing　molecules　immobilized　within　the　inner　surface　of　hollow　syringe　and　simultaneously　the　interior　space　of　hollow　syringe　substantially　increases　the　amount　of　immobilized　sensing　molecules.　This　microneedle　design　thus　extends　the　lifetime　as　well　as　improves　the　detection　sensitivity.　The　final　MGMSP　enables　the　continuous　real-time　monitoring　of　glucose　in　the　interstitial　fluid　of　live　rats.　This　innovative　microneedle-based　MGMSP　could　potentially　provide　the　public　with　high-accuracy　continual　glucose　monitoring.　©　2023　Elsevier　B.V.