This study investigates the role of phosphatidylserine (PS)-dependent ingestion of apoptotic cells in promoting TGF-β1 secretion and resolving inflammation. In vitro, macrophages induce TGF-β1 secretion upon ingesting apoptotic cells, leading to an anti-inflammatory effect. In vivo, direct instillation of apoptotic cells into inflammatory sites enhances the resolution of acute inflammation, likely through increased TGF-β1 production. This effect is specific to apoptotic cell clearance and is mediated by PS recognition and ligation of PS receptors. Apoptotic cell clearance reduces proinflammatory mediators and inflammatory cell counts in the bronchoalveolar lavage fluid (BALF). The resolution of inflammation is reversible by opsonization or neutralizing anti-TGF-β1 antibodies. The study highlights the importance of PS recognition and TGF-β1 induction in the resolution of inflammation, suggesting that apoptotic cell clearance may play a crucial role in both homeostasis and the resolution of inflammation.This study investigates the role of phosphatidylserine (PS)-dependent ingestion of apoptotic cells in promoting TGF-β1 secretion and resolving inflammation. In vitro, macrophages induce TGF-β1 secretion upon ingesting apoptotic cells, leading to an anti-inflammatory effect. In vivo, direct instillation of apoptotic cells into inflammatory sites enhances the resolution of acute inflammation, likely through increased TGF-β1 production. This effect is specific to apoptotic cell clearance and is mediated by PS recognition and ligation of PS receptors. Apoptotic cell clearance reduces proinflammatory mediators and inflammatory cell counts in the bronchoalveolar lavage fluid (BALF). The resolution of inflammation is reversible by opsonization or neutralizing anti-TGF-β1 antibodies. The study highlights the importance of PS recognition and TGF-β1 induction in the resolution of inflammation, suggesting that apoptotic cell clearance may play a crucial role in both homeostasis and the resolution of inflammation.