Background Studies on humans have related the high consumption of fructose, especially in the form of sugar-sweetened beverages, to obesity, fatty liver, and hypercholesterolemia, all risk factors for atherosclerosis, and cardiovascular disease. We aimed to determine whether supplementation of liquid fructose (SLF), in either a normal, healthy chow or a Western-style chow, promoted the appearance of atherosclerosis in a rodent model. Methods LDL receptor knockout mice were fed for twelve weeks with normal chow, normal chow plus ad libitum 15% fructose solution, Western chow, or Western chow plus ad libitum 15% fructose solution (W + F). Food and liquid intake and body weight were periodically monitored. At the end of the study, plasma and hepatic lipids, liver histology and expression of genes related to lipid handling were analyzed and histological and immunohistological analyses of atherosclerosis at the aortic origin was performed. Results Total calorie intake was significantly increased in Western-fed vs normal chow-fed mice, but was not modified by SLF. SLF significantly increased body weight, visceral adiposity, plasma lipids and liver cholesterol content in Western-fed mice, probably due to an increase in de novo lipid synthesis. Aortic atherosclerotic total lesion area was significantly correlated to plasma lipids, being highest in W + F mice. Further, SLF induced higher immunostaining for macrophages and oxidized-LDL receptor, independently of lesion area and caloric burden. Conclusions SLF, without changing total calorie intake, increases atherosclerosis, visceral adipose tissue and cholesterol burden in a background of overweight LDL receptor knockout mice consuming an unhealthy, Western-type solid rodent chow.