The ketogenic diet is becoming an assisted treatment to control weight, obesity, and even type 2 diabetes. However, there has been no scientific proof supporting that the ketogenic diet is absolutely safe and sustainable. In this study, Sprague-Dawley (SD) rats were fed different ratios of fat to carbohydrates under the same apparent metabolizable energy level to evaluate the effects of a ketogenic diet on healthy subjects. The results showed that the ketogenic diet could relatively sustain body weight and enhance the levels of serum alanine aminotransferase (ALT) and serum alkaline phosphatase (SAP), leading to more moderate lipoidosis and milder local non-specific inflammation in the liver compared with the high-carbohydrate diet. In addition, the abundance of probiotic strains such as Lactobacillus, Lactococcus, and Faecalitalea were reduced with the ketogenic diet in rats, while an abundance of pathogenic strains such as Anaerotruncus, Enterococcus, Rothia, and Enterorhabdus were increased with both the ketogenic diet and the high-carbohydrate diet. This study suggests that the ketogenic diet can lead to impairments of liver function and changed composition of the gut microbiota in rats, which to some extent indicates the danger of consuming a generalized ketogenic diet.