Background: Doxorubicin is used for treatment of solid tumors blood cancers, however, its cardiotoxicity, cardiomyopathy, and congestive heart failure, are the major limitation of its use. Doxorubicin treatment induces inflammation in various cancer cell lines. Exposure urothelial cells to doxorubicin (DOX) show an increase in IL-1β and prostaglandin E2, similarly, studies have shown that high IL-8, TNF-α and NFκB. This study aimed to investigate the effects of doxorubicin treatment of inflammatory and prooncogen mediators in heart muscle and tumor tissue. Methods: Sixty 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 three groups (20 mice per group) as follow: Control group, in which mice received an intraperitoneal (i.p.) injection of 0.2 ml normal saline once weekly on days 0, 7, 14, 21 (for 21 days), Solid Ehrlich carcinoma (SEC) control group, in which mice received an intraperitoneal injection of 0.2 ml normal saline once weekly on days 0, 7, 14, 21 (for 21 days) starting one hour after tumor inoculation, DOX group, in which mice received DOX (4 mg/kg, i.p.) once weekly on days 0, 7, 14, 21 (for 21 days) starting one hour after tumor inoculation. Results: administration of DOX to ECCs-bearing mice resulted in a significant increase in cardiac tissue IL-6 level by 4 folds compared to the control group and subcutaneous implantation of ECCs resulted in a significant increase IL-6 in tumor tissue. Administration of DOX to ECCs-bearing mice resulted in a significant decrease in tumor tissue IL-6 and TNF-α levels. SEC group showed a significant increase in tumor tissue SphK1 activity compared to the control group and administration of DOX ECCs-bearing mice resulted in the non-significant effect on the tumor tissue SphK1 activity. Conclusion: Treatment with DOX, leads to increase in inflammatory mediators as, IL-6 and TNF-α, in cardiac muscle tissue amelioration of these parameters in tumor tissue. SphK1 enzyme activity was increased by tumor induction.