Experimental results showed that cinobufagin attenuated the expression levels of p-Smad3, α-SMA, Col1a1 and Fn, indicating that cinobufagin treatment significantly maintained the balance between the degradation of ECM components in the local lung microenvironment, which is important for the amelioration of pulmonary fibrosis. Here, SMAD3 is linked to pulmonary fibrosis.