Panax ginseng (PG) has been commonly used as medicinal herb for the treatment of various diseases in Eastern Asia for thousands of years. This study was designed to investigate the protective effect of PG against paracetamol-(N-acetyl-p-aminophenol; APAP)-induced liver damage in rats. Thirty-two albino Wistar rats were divided into four groups: Group C (control); Group APAP (gavaged orally with APAP (APAP, 2 g/kg, single dose); Group PG 100 mg/kg + APAP or 200 mg/kg + APAP (these two groups were treated by gavaging with PG (100 or 200 mg/kg) for 30 days following a single dose of APAP). APAP treatment alone induced hepatotoxicity, evidenced by significant increases in malondialdehyde (MDA) level and serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-alpha (TNF-alpha). In addition, the level of GSH in the liver was significantly reduced, as were the activities of superoxide dismutase (SOD) and catalase (CAT). Liver histopathological examination showed that APAP administration induced centrilobular necrosis and infiltration of lymphocytes. However, these biochemical and histological changes were prevented by PG pretreatment. In conclusion, our results suggest that PG may be considered a protective medicinal herb against APAP-induced liver injury.