Using both in vitro and in vivo models of pulmonary fibrosis, we demonstrated that the expression of CB1R increased in lung fibroblasts in response to pulmonary fibrosis, and the pharmacologic activation of CB1R with its specific agonist ACPA protected against BLM-induced pulmonary fibrosis, significantly decreasing lung fibroblast migration and the excessive expression of ECM proteins (collagen, fibronectin, and α-SMA) stimulated by BLM in vivo or TGF-β1 in vitro, rather than the basal expression of ECM proteins in normal control lung fibroblasts. Here, TGFB1 is linked to pulmonary fibrosis.