Apoptotic cell clearance promotes TGF-β1 secretion and inflammation resolution. In this study, the ingestion of apoptotic cells by macrophages in vitro induces TGF-β1 secretion, leading to anti-inflammatory effects. In vivo, direct instillation of apoptotic cells into inflamed tissues enhances inflammation resolution. This process requires phosphatidylserine (PS) exposure on apoptotic cells and local TGF-β1 induction. PS is a key ligand for phagocyte recognition and uptake of apoptotic cells. PS-expressing apoptotic cells, such as Jurkat T cells or PLB-985 cells, induce TGF-β1 production, while PS-deficient cells do not. PS liposomes or PS-expressing cells restore TGF-β1 induction. Apoptotic cell instillation into LPS-stimulated lungs reduces proinflammatory chemokine levels and inflammatory cell counts in bronchoalveolar lavage fluid (BALF). This reduction is due to early neutrophil decrease and later lymphocyte and macrophage decrease. TGF-β1 secretion is mediated by PS recognition and PS receptor (PSR) ligation. Opsonization or TGF-β1 neutralizing antibodies reverse the anti-inflammatory effect. In vivo, apoptotic cell clearance leads to increased TGF-β1 production, which promotes inflammation resolution. The anti-inflammatory effect is specific to apoptotic cell clearance and mediated by TGF-β1. PS is crucial for TGF-β1 induction, as PS-deficient cells fail to induce TGF-β1. PS-containing liposomes also induce TGF-β1, though less effectively than whole apoptotic cells. TGF-β1 production is regulated by both preformed and de novo synthesis. The study highlights the role of apoptotic cell clearance in resolving inflammation through TGF-β1 induction, which is essential for tissue homeostasis and wound healing.Apoptotic cell clearance promotes TGF-β1 secretion and inflammation resolution. In this study, the ingestion of apoptotic cells by macrophages in vitro induces TGF-β1 secretion, leading to anti-inflammatory effects. In vivo, direct instillation of apoptotic cells into inflamed tissues enhances inflammation resolution. This process requires phosphatidylserine (PS) exposure on apoptotic cells and local TGF-β1 induction. PS is a key ligand for phagocyte recognition and uptake of apoptotic cells. PS-expressing apoptotic cells, such as Jurkat T cells or PLB-985 cells, induce TGF-β1 production, while PS-deficient cells do not. PS liposomes or PS-expressing cells restore TGF-β1 induction. Apoptotic cell instillation into LPS-stimulated lungs reduces proinflammatory chemokine levels and inflammatory cell counts in bronchoalveolar lavage fluid (BALF). This reduction is due to early neutrophil decrease and later lymphocyte and macrophage decrease. TGF-β1 secretion is mediated by PS recognition and PS receptor (PSR) ligation. Opsonization or TGF-β1 neutralizing antibodies reverse the anti-inflammatory effect. In vivo, apoptotic cell clearance leads to increased TGF-β1 production, which promotes inflammation resolution. The anti-inflammatory effect is specific to apoptotic cell clearance and mediated by TGF-β1. PS is crucial for TGF-β1 induction, as PS-deficient cells fail to induce TGF-β1. PS-containing liposomes also induce TGF-β1, though less effectively than whole apoptotic cells. TGF-β1 production is regulated by both preformed and de novo synthesis. The study highlights the role of apoptotic cell clearance in resolving inflammation through TGF-β1 induction, which is essential for tissue homeostasis and wound healing.