In the current study, the possible prophylactic and therapeutic effects of colostrum (COL) on acute organ injury caused by paracetamol (PAR) in rats were evaluated. Within the scope of this study, a 2-month-old male (150-200 g) 70 Wistar Albino rat was used and a total of seven groups were designed. The first group (CNT) was maintained for control purposes. The second group (COL-1) was given COL for 1 day, at a dose of 500 mg/kg at 6-h intervals, and blood and tissue sampling was performed at 24 h. The third group (COL-7) received COL for 7 days, at a dose of 500 mg/kg at 6-h intervals on day 1 and at a daily dose of 500 mg/kg on the following days, and blood and tissue samples were taken at the end of seventh day. The fourth group (PAR-1) was administered with PAR at a dose of 1.0 g/kg bw and was blood and tissue sampled at 24 h. The fifth group (PAR-7) received PAR at a dose of 1.0 g/kg bw on day 1 and was blood and tissue was removed at the end of day 7. The sixth group (PAR+COL-1) was administered with a combination of PAR (1 g/kg bw) and COL (500 mg/kg at 6-h intervals), and blood and tissue samples were collected at 24 h. The seventh group (PAR+COL-7) received 1.0 g/kg bw of PAR on day 1 and was given COL throughout the 7-day study period (at a dose of 500 mg/kg at 6-h intervals on day 1 and at a daily dose of 500 mg/kg on the following days). In the seventh group, blood and tissue samples were taken at the end of seventh day. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), glucose, creatinine, triglyceride, total bilirubin, total protein and albumin levels/activities were analysed in the serum samples. The malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) levels/activities, known as oxidative stress parameters, were assayed for tissue homogenates and blood (erythrocytes/plasma); in addition, enzyme activities of GSH S-transferase (GST), cytochrome P4502E1 (CYP2E1), NADH-cytochrome b5 reductase (CYTB5), glucose-6-phosphate dehydrogenase (G6PD), NADPH-cytochrome P450 C reductase (CYTC) and glutathione (GSH) levels/activities defined as drug metabolising parameters were measured in liver homogenates. In result, it was determined that PAR caused significant alterations in some biochemical and lipid peroxidation parameters and the activities/levels of drug metabolising parameters in the liver and that COL normalised some of these parameters and reduced PAR-induced tissue damage.