Objective To investigate the cytoxicity of silver nanoparticles (SNPs) and presume the mechanism.Methods In this study，SNPs were test samples and silver microparticles (SMPs) were control samples.SNPs or SMPs were cultured with L929 cells at different doses from 2.5μg/ml to 500μg/ml，respectively.After 24 hours of culture，the cells’ relative growth rates (RGRs) were tested with MTT colorimetric assay and the ultrastructures of cells were evaluated with transmission electronic microscopy (TEM).Results The cytoxicity induced by SNPs was more severe than by SMPs at the same dose (50μg/ml-500μg/ml).And a dose-effect could be observed at the SNPs’ dose between 10μg/ml and 100μg/ml (the higher the doses，the lower the RGR，the larger the cytoxicity).SNPs could be phagocytozed by L929 cells and enter into the cells，while the SMPs did not.Conclusions The cytoxicity mechanism of SNPs is different from that of SMPs and the key factor is SNPs could enter into cells yet SMPs could not.Once the dimension of silver particles is reduced to nanoscale，SNPs may have adverse effects on human health.We should be cautious with SNPs-based medical devices in clinical practice.