Background: D-galactose-induced aging animal model is similar to human natural aging. Whether the expression of protein phosphatase-1 (PP-1) in the brain of D-galactose-induced aging mice is related to cerebral aging process or not should be researched further. Objective: To investigate the effect of the APP17 peptide and the liquid extract of jiunao yizhi capsule on regulating the expression of PP-1 in hippocampal neurons of the aging mice induced by the D-galactose (D-gal). Design: A random controlled study. Setting: Department of Pathology, College of Basic Medical Sciences, Capital University of Medical Sciences and Beijing Research Laboratory for Brain Aging, Xuanwu Hospital of Capital University of Medical Sciences. Materials: The study was completed between July 2003 and July 2004 in the Experimental Center of Capital University of Medical Sciences. Forty male Kunming mice (SPF grade) with a body mass from 28 g to 32 g were purchased from Chinese Academy of Medical Sciences Institute of Material Medical. Methods: Kunming mice were randomly divided into 5 groups: control group, D-gal group, APP17 peptide treatment group, low dose herb treatment group, and high dose herb treatment group with 8 mice in each group. In D-gal group, APP17 peptide treatment group, low dose herb treatment group and high dose herb treatment group, galactose was injected subcutaneously (50 mg/kg). Meanwhile, 0.1 mL normal saline containing 0.35 μg of APP17 peptide was injected subcutaneously into the mice in APP17 peptide treatment group, once a day for 3 months; liquid extract of jiunao yizhi capsule (provided by Beijing Chaoyangmen Hospital and Shanxi Quwo Traditional Medical Institute; the main component: dangshen, baizhu, guijia and chuanshanjia, etc.) was perfused by stomach (0.3 g/kg and 1.0 g/kg respectively) in low dose herb treatment group and high dose herb treatment group, once a day. And equivalent normal saline was injected and perfused in the two control groups. After 3 months of survival, the mice were killed and their brains were cut into sections. The immunohistochemical staining of these sections was then performed with PP-1 antibody. Main outcome measures: The results of immunohistochemical staining analysis of PP-1. Results: Forty mice entered the final analysis without any loss. PP-1 positive cells in the hippocampus were poorly stained in the D-gal mice. In contrast, PP-1 positive neurons were widely distributed in the hippocampus of those normal mice, the APP17 peptide-treated D-gal mice and the high liquid extract of raw herb-treated, D-gal mice. These cells were darkly stained in cytoplasm. The unexpected result was that in the low liquid extract of raw herb-treated D-gal mice the number of PP-1 positive neurons did not increase to normal. Conclusion: The results demonstrated that the expression of PP-1 decreased in the hippocampus of D-gal mice. The APP17 and low dose liquid extract of raw herbs can regulate the distribution of PP-1 in the brain of D-gal mice and make them recover to normal situation.