One of the most important roles of cancer chemotherapy is an adjuvant to local treatment modalities such as surgery and radiation therapy. Anticancer drugs are widely used against variety of human tumors. The in vivo system provided the foundation for mass screening of novel compounds. One of the characteristics that distinguish anti cancer agents from other drugs is the frequency and severity of side effects with therapeutics doses. These drugs affect various tissues in a dose dependent manner and also show an inter–individual susceptibility. MATERIAL METHODS: The present study was conceived to evaluate effects of different doses of Methotrexate on liver of rats so that inference drawn from the study could have impact on treatment of cancer and dosage selection. RESULTS: It was found that all the Mtx treated groups (2,3 and 4) showed significant toxic changes where as the control group (1) did not reveal any changes.