Oxidative modification of low-density lipoprotein has been implicated in atherogenesis and the lipid peroxidizing enzyme 12/15-lipoxygenase (12/15-LOX) was suggested to be involved. For this study, we induced a strong and long-lasting systemic overexpression of the 15-LOX, in female New Zealand White rabbits by transient experimental anemia. After the hematopoietic parameters had returned to normal, these animals and age-matched controls were fed a lipid-rich Western-type diet for 10 weeks. Analyzing the lipid deposition in the aortic wall, we found that the 15-LOX overexpressing rabbits deposited significantly (P<0.01) less cholesteryl linoleate in the thoracic aorta than the corresponding controls. Similar results were obtained when free cholesterol and cholesteryl oleate were quantified. However, in the aortic arch where lipid deposition was much more severe a similar trend was observed, but the effects were not significant any more. Comparative determination (lipoxygenase overexpressing vs. control animals) of various plasma parameters as well as histological inspections of major organs did not reveal any indications for major organ malfunction. These data suggest that transient experimental anemia, which is accompanied by a long-lasting overexpression of the reticulocyte-type 15-LOX protects cholesterol-fed rabbits from lipid deposition in the aortic wall.