Background/Aim: The hepatoprotective role of various molecules in drug-induced hepatotoxicity arouses great interest. We investigated the effect of liposomal curcumin (LCC) on experimental acetaminophen (APAP)-induced hepatotoxicity. Materials and Methods: Rats were randomly allocated into 5 groups, and the effect of two LCC concentrations was studied: group 1 -1 ml intraperitoneal (i.p.) saline, group 2 -APAP pretreatment, group 3 -APAP+silymarin (extract of the silybum marianum with anti-inflammatory, anti-oxidant, and anti-fibrotic properties), group 4 -APAP+LCC1, group 5 -APAP+LCC2. The biomarkers of oxidative stress (nitric oxide and malondialdehyde) and antioxidant status of plasma (thiols and catalase), TNF-α, MMP-2 and MMP-9 serum levels were evaluated. Results: An improvement in oxidative stress, antioxidant status, and TNF-α, MMP-2 and MMP-9 levels was obtained in groups pretreated with LCC compared to silymarin treatment, in a dose-dependent manner. Histopathological examination reinforced the results. Conclusion: Liposomal curcumin improves the oxidative stress/antioxidant balance and alleviates inflammation in experimental APAP-induced hepatotoxicity.