Aim: It is unknown if the beneficial effects of mesenchymal stromal cells (MSC) transplantation into the liver are dependent on their anchorage and differentiation into hepatocytes or rather the result of the release of stem cell intracellular content with hepatoprotector properties. Materials & methods: The effects of intact MSC transplantation were compared with the infusion of MSC lysates in an experimental rat model of acute liver failure. Results: A more powerful hepatoprotective and antiapoptotic effect was obtained after infusion of MSC lysates than intact MSC. Changes in IL-6 levels and miRNAs might explain the beneficial effects of MSC lysates. Conclusion: Infusion of MSC lysates show a better hepatoprotective effect than the transplantation of intact MSC.