Objective To investigate the effects of high fat diet on stability of mitochondrial DNA/mRNA of frontal cortex tissue in mice.Methods Forty male mice were randomly divided into regular diet group and high fat diet group (n=20).All animals were sacrificed at 4 months (n=10) or 6 months (n=10) after experiment.The serum glucose,lipid and cholesterol levels were evaluated.And mitochondria were isolated in the frontal cortex of mice,and the changes ofmitochondrial DNA/mRNA were tested using PCR and real-time quantitative PCR.Results The serum glucose,lipid and cholesterol levels showed no significant changes in the mice of high fat diet group after feeding for 4 months as compared with those in the mice of regular diet group (P＞0.05),while the lipid level in the high fat diet group was increased significantly as compared with that in the regular diet group after feeding for 6 months (P＜0.05).The D-Loop level showed no significant changes after feeding for 4 and 6 months between the high fat diet group and the regular diet group (P＞0.05).Decreased ATPase6 and increasd Cyt3 and Cytb expression levels in the high fat diet group were noted as compared with those in the regular diet group after feeding for 6 months(P＜0.05).Conclusion The stability of mitochondrial DNA decreases in the brain of mice at the persistent feeding with high fat diet for 6 months; especially,pattem of mitochondrial mRNA expression changes obviously at early stage.