Abstract: OBJECTIVE By introducing the efflux function of P-glycoprotein(P-gp), the way to optimize the treatment of HIV-1 infection by modulation of P-gp was discussed. METHODS Searching and summarizing literatures about HIV-1 protease inhibitor and P-gp. RESULTS The effect of P-gp expression for HIV-1 protease inhibitor absorption and distribution was summarized. CONCLUSION P-gp can hamper the absorption and distribution of HIV-1 protease inhibitor. The therapeutic effect of HIV-1 protease inhibitors can be improved by modulating P-gp properly, however, the selection and use of P-gp inhibitor will be an arduous mission in the future.