Based on these observations, this in vitro study investigated the potential effect of nintedanib in downregulating the M2 macrophage phenotype and its related profibrotic role in cultured monocytes-derived macrophages (MDMs) obtained from SSc patients affected by ILD (SSc-ILD) analyzing the gene expression and protein synthesis of specific cell membrane and functional markers of M2 phenotype (CD204, CD206, CD163, and MerTK). The gene discussed is MRC1; the disease is systemic sclerosis.