Karwinskia humboldtiana (Kh) is a poisonous shrub that causes acute or chronic intoxication in animals and humans. In chronic intoxication, the main sign is the presence of paralysis. Previously we reported a model of intoxication with Kh fruit that reproduces paralysis and clinical phases in humans when they do not die; however, there are no studies that describe damage to liver in this model. The objective was to evaluate histopathological alterations in liver during chronic intoxication. Wistar rats (n=25) were divided into five groups (n= 5). Four groups were intoxicated with Kh and one received only water as a control group. Animals were euthanized at different times during paralysis evolution. Samples of liver were obtained, and processed either for light or electron microscopy evaluation. Histological, histochemistry and immunohistochemistry analyses were performed, including a morphometric analysis. Results demonstrated necrotic areas, vascular congestion and vacuoles in the cytoplasm of hepatic cells that increased during intoxication and decreased in the recovery stage. These findings were confirmed at electron microscopy level. Morphometric analysis demonstrated statistically significant difference in occurrence of necrotic cells and PCNA positive cells between control and intoxicated groups. This was not observed with TUNEL staining. These findings demonstrate that during Kh intoxication there is a severe damage in liver that is reversible. Thus, it could be suggested that Kh causes a systemic intoxication not only damage to peripheral nervous system.