To detect the expression of P-glycoprotein (P-gp), lung resistance associated protein (LRP) and multidrug resistance associated protein (MRP) in retinoblastoma (Rb), to analyze the relationship between the expression of multidrug resistant (MDR) markers with clinic-pathological factors, the correlations among these three markers, and to study the possible mechanism of multidrug resistance in Rb.It was an experimental study. Seventy-five cases of Rb were studied with immunohistochemical methods using antibodies against P-gp, LRP and MRP. The relationship between their expression and the clinicopathological features of Rb, and the relationship between the expression of these three markers were investigated.The positive expression rates of P-gp, LRP and MRP were 64.0%, 25.3%, 36.0% in Rb, respectively. The co-expression rates of P-gp and LRP, P-gp and MRP, LRP and MRP were 18.7%, 32.0%, 20.0%, respectively. All tested proteins showed significant correlation to the differentiation of the tumor (P = 0.006, 0.000, 0.000, respectively), but no correlation was found between the expression of these markers and the age or sex of the patients. Significant positive correlations were observed between P-gp and MRP expression (P = 0.001), and between LRP and MRP expression (P = 0.000).The intrinsic multidrug resistance of Rb involves the combined effects of P-gp, LRP and MRP.