Abstract: Objective:To investigate the protective effect and anti -oxidative activity mechanism of Grifola frondosa in serum, heart and liver of aged mice. Methods:The aging mice were established with D-galactose by intraperitoneal injection. Grifola frondosa was administrated to mice by gavage 100% (Grifola frondosa large dose) , 50% (Grifola frondosa small dose. After six weeks, the mice were executed. The serum, heart and liver tissue of mice were collected. The content of malondialdehyde (MDA) , activity of superoxide dismutase (SOD) , glutathione peroxidase (GSH-Px) catalase (CAT) were examined by the ultraviolet spectrophotometer detection. Results:Compared with the D-galactose model group, Grifola frondosa in different doses significantly improved the SOD, CAT, GSH-Px activities (p<0.05) and reduced the MDAcontent (p<0.01) in serum, heart and brain of mice. Conclusion:Grifola frondosa possesses anti-oxidant activity to protect body against free radical-induced damage, especially for the high dose.