Simple SummaryTransplant recipients need to use immunosuppressive therapy in order to avoid organ rejection. These drugs, unfortunately, affect numerous organs, including liver. One of the commonly observed alteration in the hepatic tissue is vacuolar degeneration. Mostly, immunosuppressive therapy is based on three drugs from different groups: calcineurin inhibitors, mTOR inhibitors, IMDH inhibitors and glucocorticoids. There is scarse data regarding the influence of multidrug immunosuppressive therapy on condition of liver, including prenatal aspect. The aim of the current study was to compare the effects of prenatal exposition of different protocols of immunosuppressants on vacuolar degeneration in the hepatocytes of livers of rats. To our best knowledge, this is the first study concerning the effect of multidrug immnunosuppression administred in utero on hepatic tissue of rats’ offspring.AbstractImmunosuppressive drugs are essential for transplant recipients, since they prolong proper function of graft; however, they affect the morphology and function of organs, including liver. One commonly observed alteration in hepatocytes is vacuolar degeneration. Numerous medications are contraindicated in pregnancy and breastfeeding, mostly due to a lack of data concerning their advert effects. The aim of the current study was to compare the effects of prenatal exposition to different protocols of immunosuppressants on vacuolar degeneration in the hepatocytes of livers of rats. Thirty-two livers of rats with usage of digital analysis of the images were examined. Area, perimeter, axis length, eccentricity and circularity regarding vacuolar degeneration were analysed. The most prominent vacuolar degeneration in hepatocytes in the aspects of presence, area and perimeter was observed in rats exposed to tacrolimus, mycophenolate mofetil and glucocorticoids, and cyclosporine A, everolimus with glucocorticoids.This is the first study that demonstrates the results of the influence of multidrug immnunosuppression distributed in utero on the hepatic tissue of offspring.