Abstract: Macroangiopathy is a complication of Type II Diabetes Mellitus (T2DM), which is mainly caused by fibrosis of blood vessels. Using T2DM rat models, we investigated whether the traditional Chinese medicine, Di-Dang Decoction (DDD), exhibited anti-fibrotic actions on great vessels. T2DM rats were randomly divided into non-intervention group, early-, middle-, late-stage DDD intervention groups and control groups, including pioglitazone group and aminoguanidine group. After administration of DDD to T2DM rats at different times, we detected the amount of extracellular matrix (ECM) deposition in the thoracic aorta. The results showed that early-stage intervention with DDD could effectively protect great vessels from ECM deposition. Considering that TGF-β1 is the master regulator of fibrosis, we further validated at the molecular level that, compared to middle- and late-stage intervention with DDD, early-stage intervention with DDD could significantly decrease the expression levels of factors related to the activated TGF-β1/Smad signalling pathway, as well as the expression levels of downstream effectors including CTGF, MMP and TIMP family proteins, which were directly involved in ECM remodelling. Therefore, early-stage intervention with DDD can reduce macrovascular fibrosis and prevent diabetic macroangiopathy.