Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are major diseases threatening human health. The formation of airway diseases associated with chronic inflammation is often accompanied by progressive airway remodeling. In recent years, in-depth studies on asthma, COPD and atherosclerosis have found that high mobility group box 1 protein (HMGB1) can affect airway or vascular remodeling by regulating the activity of smooth muscle cells. This review summarizes the regulation of HMGB1 on differentiation of smooth muscle cells; combined with the current research results, it is speculated that the involvement of protein kinase B (AKT) may play a key role in the regulation of smooth muscle or mesenchymal cells by HMGB1. Further studies will reveal more about the molecular mechanisms of asthma and COPD and find new therapeutic approaches.