Human　P-glycoprotein　(P-gp)　is　a　kind　of　ATP-binding　cassette　(ABC)　transporters.　Once　human　P-gp　is　overexpressed　in　tumor　cells,　which　can　lead　to　tumor　multidrug　resistance　(MDR).　However,　the　present　experimental　methods　are　difficult　to　obtain　the　large-scale　conformational　transition　process　of　human　P-gp.　In　this　work,　we　explored　the　allosteric　pathway　of　human　P-gp　from　the　inward-facing　(IF)　to　the　outward-facing　(OF)　state　in　the　substrate　transport　process　with　the　two-state　anisotropic　network　model　(tANM).　These　results　suggest　that　the　allosteric　transitions　proceed　in　a　coupled　way.　The　conformational　changes　of　nucleotide-binding　domains　(NBDs)　finally　make　the　transmembrane　domains　(TMDs)　to　the　OF　state　via　the　role　of　the　allosteric　propagation　of　the　intracellular　helices　IH1　and　IH2.　Additionally,　this　allosteric　pathway　is　advantageous　in　energy　compared　with　other　methods.　This　study　reveals　the　conformational　transition　of　P-gp,　which　contributes　to　an　understanding　of　the　allosteric　mechanism　of　ABC　exporters.