Objective To establish the experimental animal model of acute tubular necrosis (ATN) in rats induced by caulis aristolochiae manshuriensis (CAM) containting aristolochic acid (AA) and compare the interventional effects among ligustrazine, prednisone and benazepril. Methods Male SD rats were divided randomly into six groups, 12 rats in each group. Control group, model group, prednisone group, benazepril group, ligustrazineⅠgroup and ligustrazineⅡgroup were given respectively by gavage with 3 ml/d distilled water,5 g?kg-1?d-1 CAM decoction (CAM 2 g/ml, AA 0.54 mg/ml, AA-Ⅰ0.46 mg/ml) for 60 days, then 3 ml/d distilled water, 10 g?g-1?d-1 CAM decoction for 30 days. Two hours after CAM gavage, control group and model group were given with normal saline. Prednisone group, benazepril group, ligustrazine group and ligustrazineⅡgroup were given with prednisone 5 mg?kg-1?d-1, benazepril 1.7 mg?kg-1?d-1, ligustrazine 50 mg?kg-1?d-1, ligustrazine 150 mg?kg-1?d-1 respectively by gavage for 90 days. Histopathology of kidney tissue was examined after 90 days. Results The renal tissue of control group was normal. Light microscopy of model group revealed patchy vacuolar changes of cells from proximal convoluted tubular epithelium, disorder and loss of brush border, exfoliated epithelial cells in the lumina, exposure of areas of denuded and rupture and thickness and atrophy of tubular basement membrane (TBM), edema and infiltration of inflammatory cells in the interstitium, focal segmental proliferation of glomerular mesangial cells and increase of mesangial matrix, part thickness of interlobular arterial walls. The above abnormalities of other four groups were significantly attenuated compared to model group. Electron microscopy of model group revealed patchy vacuolar changes and fatty degeneration of cells from proximal convoluted tubular epithelium, swelling of mitonchondria, reduce of organelle, karyorrhexis, apoptosis, infiltration of inflammatory cells (phagocytes and lymphocytes) in the interstitium and infiltration of lymphocytes in the epithelium, thickness of interlobular arterial walls, stenosis of lumina. The above abnormalities of electron microscopy in other four groups were remarkably improved compared to model group as well, especially in ligustrazine II group and prednisone group. Conclusions Pathological change of ATN is confirmed in kidney tissue and the rat ATN model induced of AA is successfully established. Benazepril, prednisone and ligustrazine can attenuate the toxic effects by AA. Prednisone and ligustrazine have a better efficacy.