Objective To observe the effect of resveratrol on multidrug resistance (MDR) in human retinoblastoma cells treated. Methods RB cells in logarithmic growth phase were divided into experimental group and control group. RB cells in experimental group were cultured with different concentrations of resveratrol (6.25, 12.50, 25.00, 50.00, 100.00 mu;mol/L) for 24 and 48 hours. The proliferation (absorbance value) was assayed using methyl thiazolyl tetrazolium (MTT). RB cells were cultured with 50.00 mu;mol/L resveratrol for 48 hours. The expressions of MDR-1, cyclooxygenase-2 (COX-2)、multidrug resistance-associated protein-1 (MRP-1), glutathione-S-transferases-pi; (GST-pi;) were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The RB cells of the control group were cultured with 0.5% dimethyl sulfoxide. Results Compared with the control group, the absorbance value decreased in experimental groups (6.25, 12.50, 25.00, 50.00 mu;mol/L) in a dose dependent manner (F=4.782，P＜0.05). The difference of absorbance value between 50.00 and 100.00 mu;mol/L experimental groups was not significant (F=6.351,P＞0.05). Compared with the control group, the mRNA (t=9.170, 5.758, 4.152, 4.638) and protein (t=3.848, 5.955, 4.541, 3.514) expression levels of MDR-1, MRP1, COX-2, and GST-pi; decreased in the experimental group (P＜0.05). Conclusion Resveratrol can down-regulate the expression of MDR in RB cells.