Monocrotaline (MCT) is a pyrrolizidine alkaloid extracted from seeds of Crotalaria spectabilis that has been used to induce structural changes in the pulmonary arteries associated with progressive pulmonary hypertension in rodents. Recent studies have demonstrated that several mediators such as elastase, vasoconstrictors (Endotheline-1), vasodilators (Nitric oxide, PGI2) and cytokines (IL-1, MCP-1) play important roles in MCT-induced pulmonary hypertension, and that the changes in pulmonary hemodynamics are required for neointimal formation in pulmonary arteries. We have recently provided the evidence that macrophage migration inhibitory factor (MIF) is also involved in this model. The MCT-induced pulmonary hypertension in animals is useful as an experimental model for understanding the pathophysiology of primary pulmonary hypertension.