Objective To investigate the effects of low dose of extracellular histone on endothelial cells in infectious diseases such as sepsis. Methods The endothelial cells were treated with 10 µg/mL recombinant human histone H3/H4 complex in replacement of calf thymus histones (CTH) for various periods of time, and the morphology changes and the viability of the endothelial cells were recorded. In addition, flow cytometry was applied to identify the characteristics of endothelial cells and enzyme-linked immunosorbnent assay (ELISA) was used to detect the extracellular histones level in endothelial cells culture. Results The low dose of CTH could continuously induce endothelial cells death, cell morphological changes and function loss, which was reproduced by 10 µg/mL recombinant histone H3/H4 complex. Results of histones quantitation showed that histone can cause a series of intracellular reactions in a short period of time. Conclusions It is showed that 10 µg/mL H3/H4 can induce the toxicity in infectious disease and this level of the dose is a lower than those used in previous studies and more close to the pathological conditions.