Doxorubicin-induced myotoxicity is of particular concern for breast cancer patients. A co-treatment is necessary to prevent loss of skeletal muscle. Creatine upregulates myogenic regulatory factors, some of which are downregulated with doxorubicin treatment. The effect of creatine monohydrate supplementation on rats treated with doxorubicin, therefore, is of interest. Rats were fed either control diet or 3% creatine chow, and after two weeks, were given an i.p. saline or doxorubicin injection. Western blotting was performed to analyze the concentration of such factors in rat tissue, and an increasing trend was seen in MyoD and Mrf4 expression while a decrease in Myf5 and myogenin expression was noticed with DOX treatment. The trend of CR+DOX, within the soleus, increased Myf5 expression when compared to both CON and DOX.