Background:Acupuncture therapy is frequently used to treat Knee Osteoarthritis (KOA) in clinic, and usually used local acupoints near the diseased knees as therapeutic targets. Some local acupoints appeared sensitization phenomenon which was called sensitized acupoints, which were regarded as important therapeutic targets to get better therapeutic effect on clinic. Therefore, it is necessary to explore the biological basis of acupoint sensitization. Meanwhile, there is a lack of an analysis of the metabolism for sensitized acupoints in KOA patients. Considering that acupuncture effect could be multi-targeted, omics (such as metabolomics) may be a useful method to reveal the relationship between sensitized acupoints and clinical efficacy of acupuncture.Methods and analysis:This study is a parallel design trial. Thirty KOA patients and 30 healthy volunteers will be recruited in this study. Mechanical pain threshold will be measured by Electron Von frey in order to confirm the highest sensitized acupoints. Then collect tissue fluid from the highest sensitized acupoints by micro dialysis technical, then apply electro-acupuncture method on the highest sensitized acupoints to treat KOA patients, after 20 sessions treatments, measure and collect again. Liquid chromatography-tandem mass spectrometry method will be used to analyze the metabonomics of dialysate.Results:This study will provide a high-quality evidence to reveal the local molecular mechanism of acupuncture sensitized acupoints for patient with KOA.Conclusion:This study will provide up-date evidence of whether acupuncture sensitized acupoints have local molecular mechanism for KOA. Trial registration number: NCT03599180 (24 Jul. 2018)