In this experiment, 48 5-week-old mice were exposed to arsenic and riboflavin through drinking water. The control group, the arsenic treatment group (20 mg/L As2O3), the riboflavin treatment group (20 mg/L VB2), the arsenic and riboflavin combined group (20 mg/L As2O3+20 mg/L VB2) were set up to explore the alleviating effect of riboflavin on tissue injury caused by arsenic. The results showed that arsenic treatment caused the heart muscle fiber septa widening, fiber bundles bending, myocardial nucleus shedding, alveolar wall thickening and alveolar cavity shrinking compared with the control group. The number of cerebral cortex cells was significantly reduced and disordered, and the nuclei were dissolved and broken. The addition of riboflavin significantly reduced the damage of arsenic to heart, lung and brain. Therefore, this study confirmed that riboflavin intervention has a significant alleviating effect on the structural damage of heart, lung and brain caused by arsenic, it provides new ideas for the toxicological mechanism and prevention of arsenic poisoning.