The aim was to observe the the effect of Lishi No.5 Formula liquid extract on NGF signal transduction pathway of D-galactose induced aging of murine brain(DGAM). Kunming mice were divided into 5 groups: control group(C), DGAM group(D), Lishi No.5 Formula large dose treatment group(L), medium dose treatment group(M), and small dose treatment group(S). Immunohistochemical staining and Western Blotting for NGF, PI3K, Akt/PKB, CREB expression of hippocampal neurons were done. The expression level of NGF, PI3K, Akt/PKB, CREB in the hippocampal decreased obviously in DGAM group compared with control group, while the result of Chinese medicine groups were the same as that in normal mice. Chinese medicine Lishi No.5 Formula up-regulate PI3K signal transduction pathway of NGF in the hippocampal of DGAM group, which showed Lishi No.5 Formula liquid might contain active substance which could stimulate PI3K. This research forms basis for studying the utility elements of Lishi No.5 Formula.