To investigate the effect of advanced glycation end products (AGE) modified protein on IL-8 secretion by human endothelial cells and the role of receptor for advanced glycation end products (RAGE) in this pathological procedure. Human umbilical vein endothelial cells (HUVEC) were cultured in vitro with different concentration AGE modified human serum albumin (AGE-HSA) which had been treated with soluble receptor for advanced glycation end products (sRAGE) or not. IL-8 levels in the supernatant were determined using Liquid Chip method. RNA was extracted from the cells and RT-PCR was performed to determine the mRNA expression levels of IL-8 in each group, and GAPDH levels were served as reference during this process. The results showed that AGE-HSA increased IL-8 secretion as a dose- and time- dependent manner. Unmodified HSA had no such effect. AGE-induced IL-8 secretion was significantly inhibited by sRAGE as a dose-dependent manner, and the decrease extent was 82.4% when the cells were incubated with 500 mg/L of sRAGE. AGE-RAGE interaction upregulated IL-8 mRNA expression in HUVEC, and this effect could be blocked by pretreatment of AGE-HSA with intact sRAGE. It was proved that AGE modified protein increases the secretion of IL-8 by endothelial cells through RAGE on protein and gene levels, which maybe provide a new aspect to study the machines and treatment methods of AGE-associated diseases.