Objective To explore the effect of estrogen on cigarette smoke⁃induced epithelial mesenchymal transition（EMT）in chronic obstructive pulmonary disease（COPD）patients by regulating miR⁃21/SMAD signaling pathway. Methods The mRNA levels of miR⁃21，E⁃cadherin，α⁃SMA and vimentin，the expression of SMAD⁃ related proteins and the proliferation activity of HBE were detected by RT⁃qPCR，Western blot and MTT. Results Estrogen promoted the decrease of EMT and vitality of HBE cells induced by CSE，up⁃regulated miR⁃21 to activate SMAD pathway，promoted the decline of EMT and cell vitality induced by CSE；It activated SMAD pathway by overexpressing miR⁃21. It could promote the declines of CSE⁃induced EMT and cell viability by activating SMAD. Conclusion Estrogen can activate SMDA pathway by up⁃regulating miR⁃21 and promote COPD development by inhibiting HBE proliferation and promoting its EMT.