To investigate the role of multidrug resistance-associated protein 2 (MRP2) in the hepatic cell membrane of rats. Thirty healthy Wistar rats were divided randomly into six groups based on time of administration (2 w, 4 w, 6 w) of 20 mg/kg of sodium arsenite, and their corresponding control groups. Animals were administered every other day. Arsenic content in blood and bile were detected by atomic absorption spectroscopy (AAS), and the expression of MRP2 in the membrane of hepatocyte by Western blotting was determined. Total arsenic levels (including organic arsenic and inorganic arsenic) in blood and bile were significantly higher than control groups (P < 0.05) at all three different time points, especially in 2 w and 4 w group (16.8 and 13.8 fold greater than that in control). The expression of MRP2 increased 36.61%, 32.36%, 12.73% more respectively in 2 w, 4 w, 6 w groups than those in control groups (P < 0.05). The expression of MRP2 was correlated with total arsenic content in bile (r = 0.713, P < 0.05). Bile is one of the major routes for the excretion of arsenite and its metabolites, and the overexpression of MRP2 may play an important role in the bile excretion of them at early stage.