Abstract: Objective To determine the effects of APOE on the intracellular signal pathways mediated by different kinds of TLR. Methods We first cloned APOE gene, set up APOE tranfected stable cell line; and then detected the activity of both NF- B and AP-1 transcription factors via chemiluminescence method. Using flow cytometric analysis, we finally investigated the expression of surface molecules in the APOE transfected RAW264.7 upon exposing to LPS, PolyI:C, PGN and BDNA. Results We demonstrated that APOE not only affected the activity of NF- B and AP-1 but also regulated the expression of costimulatory molecules induced by different kinds of TLR ligands. Indeed, APOE transfected RAW264.7 showed the higher activity of NF- B and AP-1 upon exposure to LPS and polyI: C as compared with the control(p<0.05) although NF- B activity was little inhibited upon exposing to LPS（p<0.05）. While APOE transfected RAW264.6 were stimulated by PGN, PolyI:C, LPS and BDNA respectively, APOE could remarkably promote the expression of B7-H1 induced by PGN; whereas the expression of CD86, PD-1, CD11c and Gr1 were lower in these APOE transfected stable cells. However, APOE did not effectively affect the expression of these costimulatory molecules induced by LPS, BDNA and PolyI:C. Conclusion APOE could specifically affect the expression of costimulatory molecules mediated by PGN, and regulate the activity of NF- B and AP-1, implying that APOE might be involved in the regulation of TLR-mediated immune responses.