In this study, we observed upregulation of Smad2/Smad3 in macrophages after treatment with eutopic and ectopic endometrial homogenates or serum of women with endometriosis in response to LPS stimulation, whereas blockage of Smad2/Smad3 with their inhibitor SB431542 could reverse the macrophage polarization from M1 to M2, suggesting the involvement of the TGF-β-SMAD2/3 signal transduction pathway in the M1 to M2 polarization induced by both ectopic endometrial homogenate and serum of women with endometriosis. Here, SMAD2 is linked to endometriosis.