The preparation conditions of epimedium polysaccharide-propolis flavone liposome (EPL) were optimized by response surface methodology taking entrapment rates of epimedium polysaccharide and propolis flavone as indexes. The immunoenhancement of EPL prepared with optimized condition was determined taking epimedium polysaccharide-propolis flavone suspension (EPS) and epimedium polysaccharide-propolis flavone watery solution (EPW) as control. The results showed that the optimized preparation condition was as follows: the ratio of drug to lipid was 14:1, the ratio of soybean phospholipid to cholesterol was 6:1, and the ultrasonic time was 19min. EPL could significantly promote the proliferation of T and B lymphocytes singly or synergistically with PHA or LPS, mRNA expression of IL-2 and IL-6 and secretion of IgG and IgM as compared with EPS and EPW. These results indicated that liposome could significantly improve the immunoenhancement of epimedium polysaccharide-propolis flavone immunopotentiator (EPI) and would be as the suitable dosage form of EPI.