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Pro-fibrotic and pro-homeostatic macrophage phenotypes remain ill-defined, both in vivo and in vitro impeding successful development of drugs that reprogram macrophages as an attractive therapeutic approach to manage fibrotic disease. The goal to of this study was to reveal pro-fibrotic and pro-homeostatic macrophage phenotypes which could guide the design of new therapeutic approaches targeting macrophages to treat fibrotic disease. We used nintedanib, a broad kinase inhibitor, approved for idiopathic pulmonary fibrosis (IPF) to dissect lung macrophage phenotypes during fibrosis-linked inflammation by combining in vivo and in vitro bulk and single cell RNA sequencing approaches. In the bleomycin model, nintedanib drove expression of IL-4/IL-13 associated genes important for tissue regeneration and repair at early and late time points in lung macrophages. These findings were replicated in vitro in mouse primary bone marrow derived macrophages exposed to IL-4/IL-13 and nintedanib. In addition, nintedanib promoted expression of IL-4/IL-13 pathway genes in human macrophages in vitro. The molecular mechanism was connected to inhibition of the CSF1 receptor (CSF1R) in both human and mouse macrophages. Moreover, nintedanib counterbalanced the effects of TNF on IL-4/IL-13 in macrophages to promote expression of IL-4/IL-13 regulated tissue repair genes in fibrotic contexts in vivo and in vitro. Our study demonstrates the one of nintedanib's anti-fibrotic mechanisms is to increase IL-4 signaling in macrophages through inhibition of CSF1 receptor resulting in promotion of tissue repair phenotypes.