In the current study, we demonstrated that elevation of HMGB1 in BALF preceded that of TNF-α or MCP-1 (Fig. 1A), and blocking the activity of HMGB1 dampened inflammation, prevented the development of PAH, and improved survival in MCT-induced PAH rats (Fig. 3–5). This evidence concerns the gene HMGB1 and pulmonary arterial hypertension.