Parenteral nutrition-associated liver disease, a common and life-threating complication among people who require long-term parenteral nutrition, has been associated with abnormal liver function, cholestasis, steatosis and fibrosis. Intravenous soybean lipids may be associated with the development of liver disease. We therefore examined whether different doses of parenteral lipids would affect the development of liver disease, and further investigated the possible pathogenesis of it. C57BL/6J mice with a central catheter placed in the right jugular vein were divided into three groups. The control group received normal mouse chow with intravenous normal saline; The lipids group received parenteral nutrition solution (0.14 g lipids per day); the H-lipids group received parenteral nutrition solution with twice the amount of lipids (0.3 g lipids per day). Changes in body weight, serum biochemical parameters, liver histology and farnesoid X receptor gene expression in the liver were assessed. The values of serum direct bilirubin, total bilirubin and cholesterol were markedly increased in the H-lipids group at day 7. The predominant histologic finding in the H-lipids group was steatosis, and the steatosis score in the H-lipids group was much higher than in the other two groups at either day 5 or day 7. Hepatic expression of farnesoid X receptor mRNA decreased after 7 d of parenteral nutrition. High doses of parenteral lipids are more likely to develop liver disease in a mouse model of parenteral nutrition. Farnesoid X receptor may play a key role in the development of parenteral nutrition-associated liver disease.