Although fibrosis is not a prerequisite for the NASH diagnosis, it often accompanies the three recognized diagnostic hallmarks (steatosis, lobular inflammation and hepatocyte ballooning), and can be used as a grading tool for evaluation of NASH severity . In the present study, neither cellular ballooning nor fibrosis was present in any of the groups. However, increased levels of plasma haptoglobin and TIMP-1 were observed in NASH-fed rats and are considered predictors of these pathological liver changes, indicating that the NASH diet might be promising in terms of modelling more advanced stages of NASH within a relatively short time-frame. The tendency towards increased collagen deposition in NASH-fed rats further supports this. The inability of the diets used in this study to induce liver fibrosis in rats after only 16 weeks is not entirely surprising. Successful dietary induction of fibrosis in rodent models of NASH has so far mainly been associated with either genetic manipulation, forced overfeeding or diets low in methionine and choline, [51, 52], except for the guinea pig that has been shown to develop NASH after 16 weeks of high fat feeding . However, mild hepatic fibrosis in addition to a NASH-like phenotype has also been induced in C57BL/6 mice on a high-fat diet, but only after 50 weeks . In a recent study, using levels of dietary cholesterol comparable to the level in the NASH-diet in our study, development of fibrosis in Sprague–Dawley rats was observed after only 9 weeks. . However, the diets used by Ichimura and colleagues included relatively high levels of dietary cholate (2%), which is known to potently induce hepatotoxicity and upregulate specific genes related to hepatic fibrosis .