The invention relates to an azithromycin related substance and a preparation method thereof, and belongs to the technical field of synthesis of heterocyclic compounds. The preparation method comprisesthe steps: with erythromycin imide ether as a raw material, dissolving, then adjusting the pH to 4-5, adding platinum carbon as a catalyst, introducing hydrogen gas, maintaining the pressure, and carrying out heat preservation reaction, wherein the platinum carbon is pre-treated before being used as the catalyst, wherein the pretreatment comprises the steps of stirring 5% platinum carbon in waterand adding metal ions and beating for half an hour; filtering the catalyst, recovering a material liquid thoroughly and adding acetone, adding formaldehyde formic acid, controlling the pH to 5-6, carrying out heat preservation and carrying out N methylation reaction; after the reaction is finished, extracting and separating to remove a saline water layer, adding water to an organic layer and crystallizing, to obtain a crude product; and purifying, and thus obtaining the finished product. The preparation method is applied in synthesis of azithromycin and the related substance thereof, and theazithromycin not only can be used as a reference substance applied for qualitative and quantitative analysis of azithromycin impurities, but also can be conducive to improvement of the pharmacy safetyof azithromycin.