Antisense compounds, compositions and methods are provided for modulating the expression of PTEN. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTEN. Methods of using these compounds for modulation of PTEN expression and for treatment of diseases and conditions associated with expression of PTEN are provided. Such conditions include diabetes and hyperproliferative conditions. Methods for decreasing blood glucose levels, inhibiting PEPCK expression, decreasing blood insulin levels, decreasing insulin resistance, increasing insulin sensitivity, decreasing blood triglyceride levels or decreasing blood cholesterol levels in an animal using the compounds of the invention are also provided. The animal is preferably a human; also preferably the animal is a diabetic animal.