Erythropoietin (EPO) exhibits non- hematopoietic functions. Besides its hematopoietic functions, EPO has anti-apoptotic, anti-oxidant and anti-inflammatory activities. Tissue-protective EPO effect was confirmed in brain, myocardium, liver, and kidney injury. Mesenchymal stem cells (MSCs) are nonhematopoietic cells. It may be extracted from the bone marrow, dental pulp, adipose tissue, placenta, umbilical cord, or amniotic membrane. Pre-clinical and clinical evidence shows that MSCs derived can heal injured liver tissues, enhance liver functions, and reduce liver fibrosis. Material and Methods: Hundred male albino rats were classified into five groups equally. Some biochemical and Immunohistochemical studies of COX-2 were assessed in the liver tissue. Results: MSCs and EPO treatment ameliorated the toxic effect of GalN with a significant decrease in the mean level of ALAT, ASAT, and ammonia. The combination between MSCs and EPO showed more effective protection against GalN toxicity.