OBJECTIVES: To explore mechanism of Wenshen Yangan Decoction (WSYG) for improving intestinal function in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS: Sixty male C57BL/6 mice were randomized equally into control group, MPTP group, low-, medium-, and high-dose WSYG groups (daily dose 10, 20 and 40 g/kg by gavage, respectively), and selegiline group. In all but the control group, the mice received intraperitoneal injections of MPTP (30 mg/kg) for 6 consecutive days to induce subacute PD. Motor function of the mice was assessed by the pole and open field tests, and striatal tyrosine hydroxylase (TH) expression, neuronal damage and intestinal histopathology were evaluated using immunohistochemistry, Nissl staining, and HE staining. Serum levels of diamine oxidase(DAO), D-lactic acid (D-LA), lipopolysaccharide (LPS), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK) were measured by ELISA, intestinal expressions of tight junction proteins zonula occludens-1 (ZO-1) and occludin were an alyzed by immuno fluorescence staining, and intestinal barrier permeability was assessed using FITC-dextran. RESULTS: WSYG, especially at the medium and high doses, significantly improved the performance of the mice in the behavioral tests. WSYG at all the 3 doses reduced neuronal damage and Nissl body loss in the striatum and substantia nigra, its medium and high doses significantly increased TH-positive neurons in the striatum. WSYG at the 3 doses significantly decreased serum FITC-Dextran (MW 4000) level, and medium- and high-dose WSYG markedly alleviated colonic inflammatory infiltration and edema, increased the chorionic crypt ratio, and reduced loss of ZO-1 and occludin. WSYG at all the 3 doses significantly increased serum VIP and CCK levels and decreased DAO, D-LA and LPS levels in the mice. CONCLUSIONS: WSYG effectively improve motor deficits and intestinal dysfunction in PD mice possibly by up-regulating intestinal VIP/CCK and down-regulating DAO/D-LA/LPS expressions to reduce intestinal barrier permeability, thereby alleviating dopaminergic neuronal damage.