CD4+ T helper (Th) cells, especially well balanced Th1/Th2 responses, are essential regulators of the immune responses and inflammatory diseases. Arsenic is a known immunosuppressive metalloid, but its detailed effects on immune and non-immune organs are poorly understood. In the present study, mice were treated with 2.5, 5 and 10 mg kg−1 NaAsO2 intra-gastrically for 24 h. We found that arsenic exposure led to the persistent aberration of the inherent capability of Th cells to differentiate into Th1 and Th2 cells. These results might provide novel therapeutic strategies on arsenic-induced immune related diseases.