Dendritic cells (DCs) are professional antigen-presenting cells (APC) that play a central role in the initiation and regulation of immune responses. We have previously demonstrated that Lycium barbarum polysaccharides liposomes (LBPL) as immune adjuvant elicits strong antigen-specific Th1 immune responses. The purpose of this study was to investigate underlying mechanism of liposomes promoting effect of Lycium barbarum polysaccharides (LBP) on activating DCs. LBP were loaded with high entrapment efficiency (86%) into liposomes using reverse phase evaporation. LBPL activation of phenotypic and functional maturation of DCs was explored through mechanistic studies of the TLR4-MyD88-NF-κB signaling pathway and amount of proinflammatory cytokines released. We found that LBPL indeed activated immature DCs and induced DCs maturation characterized by up-regulation of co-stimulatory molecules (MHCII, CD80, CD86), production of cytokines (IL-12p40, TNF-α), and enhancement of antigen uptake. Additionally, we demonstrated that liposomes could promote LBP up-regulation of TLR4, MyD88, TRAF6, NF-κB gene and protein expression.