Background 3 . Mesenchymal stem cells (MSCs), with their remarkable capacity for self-renewal and differentiation, provide opportunities for treating many diseases, including acute liver failure. Erythropoietin (EPO) demonstrates both hematopoietic functions and anti-inflammatory properties. Its role in tissue protection has been validated across a spectrum of injuries, including those affecting the kidneys, liver, myocardium, and brain. Experimentally, acute liver injury can be induced by the well-known and often-used hepatotoxic galactosamine (GalN). Materials and Methods: Sixty-six adult male albino rats were divided into eleven groups, each consisting of 6 rats. A range of biochemical and molecular parameters were evaluated in the liver, including the expression levels of IL-6 and IL-10, NFκB activity, BAX and iNOS gene expression, alongside histological analysis using Masson’s staining technique. Results: The administration of MSCs and EPO mitigated the toxic impact of GalN by normalizing the mean expression levels of NOS, NFκB, BAX, TLR4, IL-6, and IL-10 genes. Notably, the concurrent use of MSCs and EPO provided enhanced protective effects against GalN-induced toxicity.