Objective:To investigate short-term effect of ketogenic diet on metabolism of mice. Methods:BALB/c mice were divided into two groups and placed on normal diet or ketogenic diet for 4 days. Body weight and blood glucose were monitored everyday. On the fourth day,the blood samples and livers were gathered and liver weight/body weight were calculated. Serum triglycerides(TG),total cholesterol(TC),free fatty acids(FFA),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and beta hydroxybutyric acid(β-HB)were tested. The content of TG,cholesterol and glycogen in liver were detected. The expression levels of genes related to metabolism in livers were detected by real-time PCR. Liver pathology was also examined by HE staining. Results:Short-term ketogenic diet significantly reduced blood glucose and body weight of mice. Liver weight/body weight of short-term ketogenic mice was higher than that of control mice. A four-day feeding of ketogenic diet resulted in increased TC and β-HB in blood. Meanwhile,more TG and less glycogen were detected in the liver. Real-time PCR demonstrated that hepatic genes involved in fatty acid oxidation,oxidative phosphorylation and ketogenesis were increased. Accumulation of lipid was observed in the liver of ketogenic mice under a microscope. Conclusion:Short-term ketogenic diet induced fatty acid oxidation and ketogenesis in mice. Different from long-term ketogenic mice,elevated blood cholesterol and FAS mRNA levels were observed in short-term ketogenic mice without obvious liver damage.