ABSTRACT Objective: To investigate the effect of an anti-inflammatory drug (Piroxicam) on the development of fatty streak in rabbits. Methods: Male rabbits were fed with four types of regimen: a) normal rabbit chow, b) 1% cholesterol diet c) cholesterol diet plus Piroxicam, d) normal rabbit chow plus Piroxicam. After 12 weeks, the animals were sacrificed and the aorta, as well as the right and left branches of the coronary artery were dissected, and histological processing was carried out. Samples were observed under light microscope with different magnifications. Some biochemical tests were measured before and after the treatment. Results: A significant difference was found between the two groups receiving Piroxicam-supplemented diet and the two others (p<0.05) in respect of the mean grade of fatty streaks in the right and left coronary arteries, however, progression of the lesion in aorta was not statistically significant. Conclusion: Piroxicam was found to reduce C-reactive protein (CRP), triglyceride (TG) and LDL-C; it also led to an increase in antioxidant capacity and HDL-C. It is suggested that the anti-inflammatory drug, Piroxicam, has beneficial effects in preventing the development of fatty streaks. Key words: Fatty streak, piroxicam, rabbit, inflammation.