Long silver nanowires (AgNWs, >5 μm) have shown promising applications in next generation biomaterials. However, the toxicity of long AgNWs is not well characterized in terms of their size. In this study, five AgNWs types, including SAgNW30 (length: 5-10 μm; diameter: 30 nm), MAgNW30 (length: 20-30 μm; diameter: 30 nm), LAgNW30 (length: ∼100 μm; diameter: 30 nm), LAgNW50 (length: ∼100 μm; diameter: 50 nm), and LAgNW100 (length: ∼100 μm; diameter: 100 nm), were used to investigate the size-dependent phagocytosis and cytotoxicity in macrophage. It showed that SAgNW30, MAgNW30, LAgNW30 can be fully phagocytosed by macrophages, but LAgNW50 and LAgNW100 frustrated the phagocytosis. It demonstrated that LAgNW30 can be internalized into macrophage in a curly manner. The size-dependent cytotoxicity was observed in cell viability, apoptosis, mitochondrial damage, phenotypic transition, and inflammatory response in AgNWs-treated macrophage. The AgNWs-induced cytotoxicity was depended on their length and diameter, increased gradually in the order of SAgNW30 > MAgNW30 > LAgNW30 > LAgNW50 > LAgNW100. The findings presented here will assist in the evaluation of the size-dependent cytotoxicity mediated by long AgNWs.Keywords:Cytotoxicity; Long AgNWs; Macrophage; Phagocytosis; Size-dependent.