Abstract： Objective To investigate the effect and mechanism of Ginkgo biloba extract EGb761 on protein expression in light-damaged retinal pigment epithelial (RPE) cells. Methods The human RPE cells (ARPE-19) were divided into normal control group, light damage group and EGb761 treatment group;the cells of latter 2 groups were exposed to the cold white light [(2200±300)1x] to induce light damage responses. The light-damaged RPE cells were treated with or without EGb761 (100 g/ml). The soluble protein of those cells were extracted and separated by two-dimension electrophoresis and stained by silverstaining. Different proteins in the gel were analyzed by ImageMaster and identified by MALDI-TOF-MS, and were further analyzed by mass spectrometry and bioinformatics. Results ImageMaster and MALDITOF-MS identified 25, 33 and 11 different proteins between light damage group and EGb761 treatment group, between normal control and light damage group, between normal control and EGb761 treatment group of RPE cells respectively. Mass spectrometry and bioinformatics analysis successfully identified 16 proteins, including metabolic enzymes, cytoskeleton proteins, anti-oxidation protein and other types of proteins expressed differentially. Conclusion Protein expression profiles are different between normal control group, light damage group and Ginkgo biloba extract treatment group of RPE cells. The mechanism of protective effect of EGb761 may involve cathepsin B, heat shock protein, cytochrome C reductase, and other proteins.