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Objective(s): 3,4-Methylenedioxymethamphetamine (MDMA) is one of the most popular drugs of abuse in the world with hallucinogenic properties that has been shown to induce apoptosis in  liver cells. The present study aimed to investigate the effects of pentoxifylline (PTX) on liver damage induced by acute administration of MDMA in Wistar rat. Materials and Methods: Animals were administered with saline or MDMA (7.5 mg/kg, IP) 3 times with 2 hr intervals. PTX (200 mg kg, IP), was administered simultaneously with last injection of MDMA in experimental group. Results: The concomitant administration of pentoxifylline and MDMA decreased liver injury including apoptosis, fibrosis and hepatocytes damages. Conclusion: Our results showed for the first time that PTX treatment diminishes the extent of apoptosis and fibrosis caused by MDMA in rat liver.