The present study was designed to investigate the ameliorative effect of vitamin C administration on serum alanine aminotransferase (ALT),aspartate aminotransferase(AST),Urea, Creatinine, Alphafetoprotein(AFP), Carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19- 9), in addition to tumor necrosis factor alpha (TNF-α) , Cytochromep4502E1 and Caspase-9 gene expression in colon cancer induced by 1,2-dimethylhydrazine (DMH)in rats. Forty white female albino rats were divided into four equal groups (10 each). Group I(control group):received no drugs. Group II:(DMH group): rats injected subcutaneously with DMH (35 mg/kg body weight),twice a week for 5 consecutive weeks for colon cancer induction. Group III:(protective group): rats administrated vit C(200 mg kg-1 b. wt) orally and for 4 weeks before DMH injection and continued with vit C administration daily till the end of the experiment .Group IV:(treatment group):rats injected subcutaneously with DMH then administrated Vit C for 6 weeks till the end of the experiment. Blood and colon tissue samples were collected from all animal groups at the end of the experiment. The obtained results showed that DMH injection to rats significantly increased serum(ALT, AST, Urea, Creatinine, AFP, CEA, CA 19-9) and colon tissue TNF-α and CYP2E1while colon tissue caspase-9 gene wassignificantly decreasedwhen compared to control.Administration of Vit C significantly decreased serum (ALT, AST, Urea, Creatinine, AFP, CEA, CA 19-9) in addition to TNF-α and CYP2E1in colon tissue. How every, caspase-9 gene expression showed a significant increase. Histopathological examination of colon tissue edesquamation of the colon epithelium with heavy leukocytic infiltrationin DMH group. While administration of vitamin C in colon cancer induced rats showed mild destruction of the lining epithelium with mild leukocytic infiltration in addition to mild malignancy of epithelium when compared to DMH group. These results indicated the protective effect of Vit C against DMH induced colon cancer.