Protective effects of dithiol malonate derivatives (DMDs), YH-100, YH-150 and YH-439 on carbon tetrachloride-induced hepatotoxicity were investigated in primary rat hepatocytes culture. Treatment of DMDs to hepatocytes culture did not affect total cytochrome P-450 content and ECOD and AHH activities. Protein and RNA synthesis was also similar to control. Meanwhile, DMDs significantly decreased LDH release and in vitro lipid peroxidation induced by $CCI_4$. Accumulation of cellular triglyceride and decreased secretion of VLDL from liver cells by $CCI_4$ treatment were also significantly protected.