Objective: To study the morphological characteristics of liver toxicity induced by repeated intra-gastric administration of Realgar in rats to provide a scientific evidence for safe and effective application of Realgar. Method: The rats were randomly divided into four groups:control group and Realgar 0.01

0.04

0.17 g·kg-1 groups.The rats were intra-gastrically treated with Realgar once a day for successively 90 days

while the control group was given ultra-filtrated water.Serum biochemistry indexes were measured

and pathological change of liver under microscope was observed at day 30

60 and 90. Result: In more than 40% of the liver cells in rats mild cloudy swelling

degeneration and inflammatory cell infiltration could be observed.10% to 20% of the animals appeared patchy hepatocyte swelling

eosinophilic degeneration

focal necrosis

etc. After repeated intra-gastric administration of Realgar

more than 0.04 g·kg-1 successively 90 days.50% of liver cells in 0.17 g·kg-1 group showed mild cloudy swelling and mild inflammatory cell infiltration in interstitial at day 30 after drug withdrawal.The other groups had no statistical difference compared with the control group.2 and 3 months after intra-gastric administration of Realgar

the APTT in the experimental groups was significantly shorter than the control group.Administration for 3 months and 1 month after withdrawal

the PT also significantly shorten.The biochemical indexes in each group had no significant difference compared with the control group. Conclusion: After repeated intra-gastric administration of Realgar more than 0.04 g·kg-1 successively 90 days

the early and mild liver toxicity was observed

which can gradually returned to normal after Realgar withdrawal.