Compositions and methods are provided for modulating the expression of protein kinase C. Oligonucleotides are provided which are targeted to nucleic acids encoding PKC. The oligonucleotides are from 5 to 50 nucleotides in length and in one referred embodiment are from 12 to 18 nucleotides in length. The oligonucleotides may be chimeric oligonucleotides and in a preferred embodiment comprise at least one 2'-O-methoxyethyl modification. Pharmaceutical compositions comprising the oligonucleotides of the invention are also provided. Methods of inhibiting protein kinase C expression and methods of treating conditions associated with expression of protein kinase C using oligonucleotides of the invention are disclosed.