A Synthesis route of 2-mercapto-5-methoxyimidazo[4,5-b]pyridine was discussed. The router was : 2,6-dichloropyridine as the starting material was reacted with methanol/sodium hydroxide, after treated by potassium nitrated/concentrated sulfuric acid, then ammoniation to give 2-amino-6-methoxy-3-nitropyridine(III) which was finally reduced by tin chloride under 75℃ for 4h and cyclized by carbon disulfide to give the target compound .The overall yield reached 43.6%. The structure of product was characterized by IR, 1H-NMR and MS spectra.