Objective To investigate the effect of 8- hydroxydihydroberberine and berberine on multidrug resistance gene using Caco- 2 cell model. Method The damage of 8- hydroxydihydroberberine and berberine to Caco- 2 cell was evaluated by the MTT method. Expression of multidrug resistance gene including mdr 1,mrp 1 and mrp 2 was determined by quantitative real time PCR. Result 8- hydroxydihydroberberine and berberine had no damage to the growth of the Caco- 2 cells in the concentrations of 1 ~ 100 μM. 8-Hydroxydihydroberberine and berberine had the same effects on the expression of mdr 1 and mrp 1 gene. Berberine significantly decreased the expression of mrp 2 gene in the concentration of 25 ~ 100 μM,but there was no effect in 8- hydroxydihydroberberine-treated groups. Conclusion The difference on the expression of mrp 2 of 8- hydroxydihydroberberi- ne and berberine may imply to further study the effects on the proteins and the relationship of them.