Investigation were carried out on the permeation of lisinopril across excised rat skin for selecting a suitable solvent system for the development of a topical gel formulation. The solubility of lisinopril in pure and mixed solvents (propylene glycol: ethanol: water :: 50:30:20 for S1; 40:40:20 for S2 and 30:40:20 for S3) was determined and in vitro permeation studies for lisinopril from various pure and mixed solvent systems were carried out for enhancing the delivery of lisniopril through skin. The solubility of lisinopril in water, propylene glycol and ethanol was 98.47 mg/ml, 14.2 mg/ml and 1.01 mg/ml respectively, indicating a higher solubility in water than propylene glycol and ethanol. The solubility of the drug in ternary systems S1, S2 and S3 was 60.56, 50.32 and 33.22 mg/ml, respectively. The highest solubility of drug in a ternary system was in S1 system, which was approximately 1.2 and 1.8 times more than that in S2 and S3, respectively. The steady state flux of lisinopril across rat skin using water, propylene glycol and ethanol was 10.18 ± 1.03, 3.21 ± 0.91 and 2.01 ± 0.23 ?g/cm2/h respectively. The skin permeation rate of lisinopril from the S1 mixture was found to be higher as compared to other solvent systems (S2 and S3). The steady state flux of lisinopril across rat skin from S1, S2 and S3 was 14.32 ± 1.98, 13.67 ± 1.68 and 9.32 ± 1.76 ?g/cm2/h respectively. The result indicated that the ternary solvent system of S1 is suitable for use as vehicle for developing a topical formulation of lisinopril.