Abstract: A novel synthesis method of protocatechuic acid-(¹³COOH) was designed. 3,4-dimethoxy bromobenzene as raw material, Grignard reagent was prepared by Grignard reaction, then passed through the ¹³C labeled ¹³CO₂ gas, the intermediate 3,4-dimethoxy benzoic acid-(¹³COOH) was prepared. The crude product was obtained viademethylation with BBr₃, which was decolorizing by activated carbon. Protocatechuic acid-(¹³COOH) was obtained by cooling crystallization. Synthesis route had the advantages of simple operation, short process flow, less side product, the yield was more than 45%, ¹³C labeled isotope abundance was not diluted. The product was characterized by HPLC, MS, ¹H NMR and ¹³C NMR, the chemical purity was more than 99%, ¹³C enrichment was more than 98%. As an important tracer, it can provide a basis for medical and chemical research.