Objective: The objective of this work was to investigate the hepato-nephroprotective activity of Nigella sativa (Ranunculaceae) oil on paracetamolinduced New Zealand rabbits (Oryctolagus cuniculus). Methods:Hepato-nephroprotective activity of Nigella sativa oil was demonstrated on six groups of paracetamol-induced New Zealand rabbits (Oryctolagus cuniculus) aged 3-4 mo, three in each group (2 males, 1 female). Group I was normal control (water 1.0 ml/kg of body weight per oral), group II was negative control (water 1.0 ml/kg of body weight per oral), group III was positive control (silymarin 100 mg/kg of body weight per oral), group IV-VI were treated with Nigella sativa oil (NSO) dose of 0.5 mg/kg of body weight, 1.0 mg/kg of body weight, and 2.0 mg/kg of body weight per oral, respectively, for 15 d. At the 16 th day, rabbits in group II-VI were induced with paracetamol at a dose of 600 mg/kg of body weight per oral. At the 23 rd Results: Paracetamol administration dose of 600 mg/kg of BW resulted in the elevation of serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and ureum-N levels of the animals, particularly in group II which was treated only with paracetamol. Normal histology of the liver defines the clear shape of the terminal hepatic venule (THV)/central vein (CV) and sinusoids, whereas that of the kidney defines clear shape of the Bowman capsule and glomerulus shape. Qualitative histological examination of the liver showed that the THV/CV in all groups was normal, however in the paracetamol-treated group, the sinusoids were dilated, necrosis and mass apoptosis were detected. Dilated sinusoids were observed in the silymarin group and in the lower and medium doses of NSO groups. In the highest dose of NSO group the THV/CV and sinusoids were normal, but a local apoptosis and fat degeneration were detected. Qualitative histological examination of the kidney indicated that there was no abnormality of the glomerulus shape, however, mass apoptosis and local necrosis of the kidney were found in the paracetamoltreated group and the silymarin-treated group. The lowest dose of the NSO-treated group showed a normal shape of glomerulus and Bowman capsule, normal apoptosis. No necrosis was observed in the rabbit's kidney. Higher doses of NSO groups indicated a normal glomerulus shape and Bowman capsule, mass apoptosis and local necrosis. day the animals were measured for their clinical biochemistry parameters and histological examination. Conclusion:In this study, Nigella sativa oil could maintain the normality of the THV/CV and sinusoids in the liver of paracetamol-induced New Zealand rabbits (Oryctolagus cuniculus). Normal glomerulus shape and Bowman capsule were also confirmed in the kidney of paracetamol-induced animals.