Indole-3-carbinol (I3C) and its metabolites were proven to suppress the proliferation of various cancer cell lines by targeting a wide spectrum of signaling pathways that regulate hormonal homeostasis, cell cycle progression, and cell proliferation. Moreover, I3C inhibited tumorigenesis in mammary glands, liver, lung, and gastrointestinal tract in different animal models. These preclinical findings demonstrate the value of I3C in cancer prevention and therapy, which has led to its trial in cervical dysplasia, breast cancer, leukemia and recurrent respiratory papillomatosis. This study aimed to investigate the effects of different doses of I3C on inflammatory mediators, IL-6 and TNF-α levels and prooncogenic mediator, SphK1 activity, in tumor tissue in Solid Ehrlich Carcinoma (SEC) Tumor Model. Eighty BALB/c male mice were used in this study. Except for mice in the control group, each mouse was implanted subcutaneously with 0.2 ml of the ascites fluid containing 1x106 Ehrlich carcinoma cells (ECCs) into the thigh of the hind limb. Mice were divided into four groups (20 mice per group) as follow: Control group, Solid Ehrlich carcinoma (SEC) control group, Indole-3-carbinol (I3C 1000 ppm) group, in which mice were put on a diet containing 1000 ppm I3C starting seven days before and continued for 42 days after tumor inoculation, Indole-3-carbinol (I3C 2000 ppm) group, in which mice were put on a diet containing 2000 ppm I3C starting seven days before and continued for 42 days after tumor inoculation. Administration of I3C (1000 and 2000 ppm) to ECCs-bearing mice resulted in significant decrease in tumor volume and increased survival rate. Subcutaneous implantation of ECCs resulted in significant increase in tumor tissue SphK1 activity, TNF-α and IL-6 levels and administration of I3C (1000 and 2000 ppm) to ECCs-bearing mice resulted in significant decrease in all of these oncogenic and inflammatory mediators.