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We attempted to create a pig model of complex arterial lesions through the percutaneous injection of cholesteryl linoleate into the vessel wall.A total of 81 arterial segments (27 arteries) underwent percutaneous intramural injection of cholesteryl linoleate, in eight pigs. Intravascular ultrasound (IVUS) analysis and corresponding histology were obtained for analysis at 2 and 4 weeks after injection. Overall, 18 out of 27 (67%) of the injected arterial segments displayed lesions identifiable by IVUS as an eccentric echolucent zone present within the deeper layer of the lesion. Quantitative IVUS analysis demonstrated that these lesions were non-occlusive (36±8% area stenosis), eccentric (eccentricity index, 0.78±0.07) and located into positively remodeled vessels (remodeling index, 1.45±0.24). By histology, these lesions were eccentric and comprised less than a third of the vessel circumference. Medial thickening and a thickened intima containing lipid droplets and mononuclear cells were consistently found. The presence of lipids or local wall thickening seen by histology colocalized with the presence of echolucent structures seen by IVUS in 65% of the coronary segments and 70% of the iliac segments.The intramural deposition of cholesteryl linoleate results in the development of complex, lipid-containing inflammatory lesions in less than 4 weeks. These lesions are already identifiable by IVUS at 2 weeks and colocalize with histologic findings. Further development of this model may allow the validation of technologies designed to detect and treat high-risk atherosclerotic lesions.