[Objective] To investigate the effect of cordyceps sinensis (CS) on expression of uncoupling protein-2 (UCP2) and so to elucidate the role of UCP2 in development of nonalcoholic fatty liver diseases (NAFLD). [Methods] Rats were administrated with high-fat diet to produce NAFLD animal model and intervened by cordyceps sinensis. Triglyceride (TG), total cholesterol (TC) in liver were measured by biochemistry, adenosine triphosphate (ATP) by luciferin-luciferinase, and UCP2 expression by Northern blotting and immunohistochemistry. Liver histopathology was evaluated. [Results] High-fat diet fed rats developed obesity and showed a gradual increase in body weight, liver index, and a decrease in ATP level. More advanced liver disease was found histopathologically for longer high-fat diet. Up-regulation of liver UCP2 by high-fat diet stopped after week 12. However codyceps sinensis induced UCP2 up-regulation continuously, and kept liver ATP a relatively high level. [Conclusion] NAFLD rat models were produced successfully. Liver UCP2 up-regulation in NAFLD rats may be a definite beneficial adaptation to lipid exposure. Cordyceps sinensis may serve a protective role to prevent NAFLD from progression. One of the possible mechanisms involves in modulating UCP2 expression and thereby, regulating fat metabolism, energy homeostasis.