In recent years, chronic arsenic toxicity due to drinking of arsenic contaminated groundwater has become a worldwide public health problem.However, its toxic effects and pathogenic mechanisms remain unclear, especially at low concentrations.And so far, there is still no effective treatment for this disease.The purpose of this study was to examine changes of the erythrocyte and RBC membrane proteins in male rats exposed to low-level arsenic (10, 60, 360μg/L) through drinking water and to further explore the potential biomarkers of chronic arsenic poisoning.The RBC toxic effects were detected by different indicators and methods, including RBC parameters (Automated Hematology Analyzer),eryptosis rate (Flow Cytometry), erythrocyte morphology (Scanning Electron Microscopy).Erythrocyte membrane proteins were analyzed by sodium dedecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Immunofluorescence Assay (IFA).The results revealed that, compared with the control group, RBC parameters have not abnormal changes in exposure groups, but eryptosis rate increased significantly in 360μg/L arsenic exposure group.In the As treatment groups, and particularly in 360μg/L group, we observed more irregular-shaped erythrocytes and spheroechinocytes.Electrophoretic analysis showed decreased ankyrin expression and increased band 3 expression in 360μg/L dose group.Immunofluorescence confirmed that band 3 and CD35 increased and clustered to the RBC membrane in rats exposed to arsenic.This study suggests that low levels of arsenic exposure can produce toxic effects on erythrocyte, resulting in increased eryptosis and abnormal RBC morphology, which may be related to erythrocyte membrane proteins abnormalities.Erythrocyte membrane proteins are more sensitive to low-level arsenic than RBC number and morphology.Erythrocyte membrane proteins may be the early biomarkers in patients of chronic arsenic poisoning.