Colon cancer is one of the most common malignancies with significant importance. Recent theories believe that cancers are metabolic diseases. Therefore, the role of metabolism in the prevention and treatment of cancer has been considered and the ketogenic diet is one example. In the present study, we evaluated the effect of the ketogenic diet and a high carbohydrate diet on tumor size and number, histopathology, and insulin level as well as VEGF level in 1, 2 dymethylhydrazine (DMH)-induced colon cancer in rats. Forty adult male Wistar rats were divided into four groups as follows: control, colon cancer, ketogenic diet, and high carbohydrate diet groups. For induction of colon cancer, 30 mg/kg of 1,2 DMH solution was injected subcutaneously twice a week for 24 weeks. The results showed that the ketogenic diet reduced tumor size, number, and histopathological changes as well as VEGF level (P<0.01) compared to the colon cancer group. The ketogenic diet also increased the levels of beta hydroxyl butyrate (P<0.001) and decreased those of glucose, insulin and HbA1c (P<0.001). Furthermore, a high carbohydrate diet did not show any protective effects on colon cancer prevention. In conclusion, the ketogenic diet demonstrated prophylactic effects on colon cancer, and this anti-cancer effect could be partially attributed to the reduction in VEGF and insulin levels.