Inhibition of ADRB2 attenuated bleomycin-induced pulmonary fibrosis in mice and reduced lung fibroblast-to-myofibroblast differentiation, proliferation, and migration by modulating TGF-β signaling activity through moderation of the stability of SMAD2/3, while NAC inhibited ADRB2 mediation of TGF-β signaling. Here, SMAD2 is linked to pulmonary fibrosis.