The purpose of this research is to develop a novel liposome-mediated system for delivery of expression plasmid into specific regions in the rat brain. . Complexes of plasmid DNA and different liposome were prepared in phase 1 of the study. The composition , method of preparation were varied and the physico-chemical characterization of the different systems were investigated two different methods of preparation were used, in the first method the liposome were prepared simultaneously with the DNA entrapped into the liposome and in the second method, the liposome were prepared first and then complexes with the DNA were performed. The liposome formulations were composed of DOTAP:Cholesterol; and DC-Chol:DOPE and different lipid helpers . The particle size of liposomes prepared with DNA entrapped into the liposome were larger than those prepared with liposome-DNA complexation. All liposome formulations were spherical, uniform in size and have smooth surface. In vitro DNase digestion experiments demonstrated that liposome protect 60-80% plasmid DNA from DNase digestion. The plasmid:DNA lmediated liposome can be widely prepared, have less risk than the use of viral vectors, can protect DNA fron DNase digestion, none toxic and therefore can be used repeatedly in vivo.