Livers of WT and Cyp2e1-null mice fed LFD look grossly (not shown) and histologically normal, although some occasional fat deposits were observed in the WT-LFD (Figs. 1A and B). In contrast, livers from both WT and Cyp2e1-null mice fed HFD exhibited much paler color compared with those of their corresponding LFD controls. Histological analysis (Figs. 1C and D) revealed accumulation of micro- and macro-vesicular intracellular lipid droplets in WT-HFD and to a lesser extent in Cyp2e1-null-HFD mice and the degrees of steatosis were markedly higher than their corresponding LFD groups (Figs. 1A–D,I). However, several inflammatory foci were monitored only in WT-HFD group (Fig. 1C). According to the histological scoring system for NAFLD which reflects the sum of steatosis, hepatocytes ballooning, and lobular inflammation [14], only the WT-HFD group achieved a NAS of 5 (Fig. 1E–H). These results were supported by the measurement of hepatic triglyceride (TG) contents where TG content in HFD-WT was the highest and significantly different from those of all other groups (Fig. 1I).