Abstract: Objective To explore the influence of exposure to sodium arsenite(iAs³⁺) on protein disulfide isomerase (PDI) in skin tissues of rabbits and discuss the relationship between arsenic poisoning on skin and PDI. Methods A total of 30 healthy male rabbits was divided into 5 groups including contrast (C) group, low-dose group (L, 0.13 mg/kg·w), medium-dose group (M, 0.26mg/kg·w), medium-high-dose group (MH, 0.65mg/kg·w), and high-dose group (H, 1.30 mg/kg·w) treated with the above different doses of sodium arsenite, 6 rabbits for each group. After free drink water had been poisoned for consecutive 3 months, these animals were killed and the skin tissues on the same place of these rabbits' back were taken for sampling. Differential expression proteins between arsenite poisoning groups and contract group were screened using two-dimensional gel electrophoresis (2-DE) and identified by MALDI-TOF-MS. The expression level of PDI mRNA of skin samples of rabbitss were tested through Real-Time Quantitative PCR. Results After being poisoned for 3 months, no rabbit died, coarse fur of rabbits' back and belly were observed in M, MH, and H groups, and this condition was especially obvious in H group. It was discovered that the expression quantity of PDI was reduced in M and MH groups while was increased in H group. The expression level of PDI mRNA was increased in MH and H groups (F=225.83, P<0.001). Conclusions Sodium arsenite poisoning can change PDI mRNA and the protein expression quantity in skin tissue of rabbits. With the increasing of exposure doses, PDI mRNA expression was increased, and meanwhile coarse fur of rabbits was discovered. However, PDI protein expression was first decreased and then increased. This suggests that PDI might play a role in that arsenite damages skin.