The present study is aimed at assessing the chronic toxic effects of arsenic trioxide on liver and intestine of the zebrafish. For this purpose, histopathological changes in the liver and intestine tissues of adult zebrafish exposed to waterborne arsenic trioxide concentrations (50ppb and 500ppb respectively) for 90 days evaluated. Activation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) was also assessed by immunofluorescence assay. We observed severe histopathological alterations, including cellular degeneration, vacuolization of hepatocytes, and an increase in the hepatic plate in the liver. Histopathological changes in the intestine includes vacuolization of the enterocytes, hyperplasia of goblet cells, displacement of the lamina propria, and disruption of the apical cytoplasm of epithelial cells that cover the intestinal villi were observed. Strong signs of immunofluorescence reaction for 8-OHdG in the exposed liver and intestine tissues in a dose-dependent manner has also been detected. Results of the study indicate that toxicity of arsenic trioxide lead to crucial histopathological alteration and induce oxidative DNA damage in both liver and intestine of zebrafish.