Background: Diethylnitrosamine (DEN) is a hepatotoxin whose metabolic activation by liver cytochromes P450 is responsible for the necrosis, mutagenicity and carcinogenicity of liver cells. The purpose of this study was to evaluate the protective effects of Calotropis procera roots bark against DEN induced hepatocellular damage in rats. Material and Methods: Hepatoprotective activity of the ethanolic extract of Calotropis procera root bark were evaluated by induction of liver injury with DEN in Wistar male rats distributed in six groups of six. Serum hepatic markers, alanine amino transferase (ALAT), aspartate amino transferase (ASAT), alkaline phosphatase (ALP), total protein and albumin were evaluated and the enzymes antioxidant activities, superoxide dismutase (SOD) and catalase, as well as the level of malonedialdehyde (MDA) were determined in the liver homogenate. Histological analysis was carried out on sections of rat livers. Phytoconstituents have also been studied. Results: Pretreatment of rats with the extract showed a significant decrease in ALAT, ASAT and ALP while there was an increase in total protein and albumin compared to rats treated only with DEN. It also showed a significant increase in SOD and catalase and a decrease in MDA levels suggesting the hepatoprotective effect of the extract. Observation of liver sections confirmed the results of the biochemical parameters which would attest that the extract is hepatoprotective. Phytoconstituents such as sterols, triterpenes and phenolic compounds have been demonstrated. Conclusion: Ethanolic extract of Calotropis procera roots bark has shown hepatoprotective effects that could be due to its content in sterols and triterpenic and phenolic compounds.