For the first time, we demonstrate that the expression of Sirt2 is increased in lung fibroblasts stimulated with TGF-β1 in vitro and in the mice model of pulmonary fibrosis induced by bleomycin in vivo; inhibiting Sirt2 by the pharmacologic inhibitor or targeting small interfering RNA can inhibit fibrosis process by blocking Smad2/3 signaling pathway. Here, SMAD2 is linked to pulmonary fibrosis.