insulin growth factor-1 (iGF-1) is an endocrine regulator that plays an important role in normal growth and development. iGF-1 mediated effects may result in protecting macrophages from immunometabolic response. However, it is unclear whether iGF-1 has a protective effect on fatty acid-induced macrophages damage. in the present study, THP-1 cells were differentiated into macrophages and stimulated with palmitic acid (Pa) in the absence or presence of iGF-1. Macrophages apoptosis was measured by cell counting Kit-8 assay, flow cytometry, Hoechst 33342 staining and western blotting. The mitochondrial damage was evaluated using Jc-1 staining and mitochondrial reactive oxygen species detection. The activation of mitophagy was assessed using immunofluorescence and western blotting. As a result, IGF-1 significantly restored the survival rate in macrophages, while the apoptosis was inhibited through mitochondrial pathway. in addition, iGF-1 protected the mitochondrial damage induced by Pa. Furthermore, Pa induced mitophagy via phosphatase and tensin homolog-induced putative kinase protein 1/Parkin, which was reversed by iGF-1. Taken together, the present study demonstrated the protective effect of iGF-1 on Pa-induced mitochondrial apoptosis in macrophages, which might provide a potential therapeutic strategy for treatment of lipotoxicity.