Abstract: ［Abstract］Objective　To investigate the expression of 3-phosphoinositide-dependent protein kinase 1（PDK1） in skeletal muscle tissue of hyherhomocysteinemia animal model， to explore the effect of homocysteine on glucose uptake．Methods　Twenty healthy mice，six weeks of age，were randomly divided into control group（n = 10）and high hyperhomocysteinemia group（n =10）．Normal food was fed in control group；Normal food and 1.5 % （mass fraction）methionine were fed in hyperhomocysteinemia group．After the feed in the hyperhomocysteinemia group and the control group were fed for three months，the levels of blood glucose were determined in the feeding． The variations of PDK1，phosphorylation of PDK1 and phosphorylation of Akt were observed with Immunohistochemistry in skeletal muscle cells．The expressions of PDK1，phosphorylation of PDK1，Akt and phosphorylation of Akt were determined with Western Blot in skeletal muscle tissue．Results　The feeding plasma glucose in the hyperhomocysteinemia group were higher than that in the control group（P＜0.05）．The gray values of PDK1，p- PDK1（Ser-241）and p-Akt（Thr-308）were increased in the herpyhomocysteinemia group with Immunohistochemistry compared with the control group（P＜0.05）．The levels of PDK1，p- PDK1（Ser-241）and p-Akt（Thr-308）were the lower in the homocysteinemia group with Western Blot（P＜0.05）．However，the expression of Akt protein was not difference between the homocysteinemia group and the control group（P＞0.05）． Conclusion　Homocysteine may decrease the expression of PDK1 and phosphorylation of PDK1 in skeletal muscle tissue，thus inhibits glucose uptake.