The hepatocytes were cultivated in the presence of lithium carbonate (LC) for drugs testing or possible source for transplantation in the treatment of hereditary or terminal liver diseases. The LC, as an inducer of autophagy, is a promising drug for maintaining cell homeostasis and has a significant effect on the ultrastructural organization of hepatocyte cells. Within current investigation, new mechanisms of the biological effects of lithium and the ultrastructural analysis of the primary culture of hepatocytes were studied via flow cytofluorometry, light, and electron microscopy methods. Obtained results demonstrate the absence of the toxic effect of 5 mM of LC on the primary hepatocyte culture. In addition, LC does not block the cell cycle at the G(0)/G(1) stage after 24 h of hepatocyte cultivation and promotes the preservation of their viability by 48 h of the experiment. Moreover, LC does not stimulate hepatocyte apoptosis, induces autophagy and the preserves the proliferative activity of hepatocytes. (C) 2020 Elsevier Inc. All rights reserved.