Silymarin, a standardized extract from Silybum marianum seed, is a natural hepatoprotector used for the treatment of liver diseases in man. The aim of this study was to investigate its safety and efficacy in periparturient dairy cows. Ten treated and 10 control pregnant dairy cows were paired by parity, body condition score (BCS), health condition and previous milk production. Treatment consisted of daily 10 g per animal of silymarin extract administered as oral drenches, from 10 days prior to the calving date to 15 days after calving. Blood samples and liver biopsies were taken from each animal at 7 and 30 days after calving. Hepatic functions were evaluated by assay of plasma beta-hydroxybutyrate (BHBA), total cholesterol, high-density lipoproteins, low-density lipoproteins, triglyceride and total bilirubin. The histological aspect of the liver was assessed in biopsies. Clinical chemistry values were similar for both groups and effects at different times (day 7 versus day 30; P < 0.05) were attributed to physiological variations in periparturient cows. Histology showed fat accumulation in the liver of both groups, as it is expected in periparturient dairy cows. In treated cows, fat-rich hepatocytes were observed near the central vein. These observations suggest that, at the used dosage, S. marianum extract has no adverse effect on the liver of lactating cows, and presents no objective evidence for a hepatoprotective effect in this species.