Purpose: This study was carried out to evaluate effect of aqueous and hydroethanolic extracts of Secamone afzelii leaves on Liver transaminases, serum vitamin D and Zinc levels in hepatotocixity induced by carbon tetrachloride (CCl4) in rats. Methods: The experiment was performed on 7 groups of 6 rats by the method of Mekky and collaborators. Rats were pre-treated with aqueous, hydroethanolic extracts Secamone afzelii (100 and 200 mg/kg) and Silymarin (SIL) an hepatoprotective reference prior to CCl4. Hepatotoxicity was induced by the intraperitoneal injection of Carbon tetrachloride (CCl4) in rats. Hepatotoxicity implied a significant rise of Liver transaminases (ALT and AST) by hepatocyte alteration rate. The parameters evaluated in the study were alanine aminotransferase (ALT), aspartate aminotransferase (AST), vitamin D and Zinc in serum. Vitamin D and Zinc levels in serum were respectively determined by HPLC analysis and Atomic absorption method. Results: Carbon tetrachloride injection to rats every 2 days showed a significant rise of Liver transaminases (ALT and AST) and a significant lowering of vitamin D and zinc levels in serum compared to normal. However, pre-treatments with aqueous and hydroethanolic extracts of Secamone afzelii caused a significant decrease of Liver transaminases (ALT and AST) and restored vitamin D and zinc levels in serum of animals (P < 0.001 and P < 0.01) compared to rats treated with CCl4 only (Negative control). Moreover, hydroethanolic extract (200 mg/kg) and Silymarin both reduced very well carbon tetrachloride effects by protecting Liver. Conclusion: This study reveals that Secamone afzelii leaves extracts (aqueous and hydroethanolic) possess protective properties of the Liver. It also shows a significant association between low serum vitamin D and zinc levels and hepatotoxicity. The most active extract is Hydroethanolic extract at the dose of 200 mg/kg which can be used for preventives purposes.