AIM: To analyze the expression of uncoupling protein 2 (UCP2) in retinal pigment epithelium (RPE) cells at the different human age, further explore the possible new target of RPE cells protection. METHODS: Adult retinal pigment epithelial-19 (ARPE-19) cells and the primary RPE cells at the different age (9-20y, RESULTS: Cells from the donors more than 60y are larger and more fibroblastic in appearance compared to ARPE-19 cells and those primary cultures obtained from the younger individuals by using phase-contrast micrographs. Results of RT-PCR, Western blot and confocal microscopy all showed that UCP2 was highly expressed in ARPE-19 cells and in the younger primary cultured human RPE cells at the age of 9-20y and 50-55y, whereas lower expression of UCP2 was measured in the older primary cultured human RPE cells at the age more than 60y. CONCLUSION: Expression of UCP2 gene is decreased in aged RPE cells, promoting the lower ability of anti-oxidation in these cells. It is indicated that UCP2 gene might be a new target for protecting the cells from oxidative stress damage.