Aim To study the inhibitory effect of chitosan on peroxidation and monocytes adhesion to vascular endothelial cells induced by high concentration of glucose. Methods Human umbilical vascular endothelial cells (HUVEC) were treated with high glucose, and high glucose with different concentrations of chitosan for 24 h. Hydroxyl radicals (OH?) and malon-dialdehyde (MDA) were measured. Monocytes Raw 264.7 were pre-incubated with Rhodamin123, and then co-cultured with HUVEC for 30 min, followed bymicroscope observation and determination of the monocytes adhesion. Finally, the mRNA expression of vascular cell adhesion molecular-1 (VCAM-1) was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Results Concentrations of OH? and MDA in HUVEC increased after incubation with high glucose. Both of the amount of adhesive monocytes and mRNA expression level of VCAM-1 in HUVEC were induced by high glucose. Inversely, chitosan inhibited these changes in a dose-dependent manner without any cytotoxicity to cells. Conclusion Chitosan can scavenge free radicals and prevent peroxidative injury on vascular endothelial cells, which further down-regulates the expression of VCAM-1 and consequently inhibits the adhesion of monocytes to endothlial cells.