Atorvastatin is a lipid lowering agent and widely used to treathypercholestermia. However following oral administration, the bioavailability of thedrug is only 12% due to extensive first pass metabolism. The aim of the current researchwas to formulate ATO- transdermal patches utilizing various polymers combinations. Hydroxypropyl methylcellulose with either eudragit RS100 or Polyvinylpyrrolidone were mixed in different ratios, in presence of polyethylene glycol 400 as plasticizer. The patches were prepared by solvent evaporation method. Physicomechanical parameters such as, drug content, patch thickness, tensilestrength, moisture loss and moisture gained were evaluated. Additionally drug excipient compatibility was assessed by FTIR and DSC. In vitro drug release was measured in phosphate buffer pH 7.4 at 37 °C. Finally,biochemical evaluation of the best formulae was evaluated on hyperlipidemic-induced rats. The results indicated that, Hydroxypropyl methylcellulose: Polyvinylpyrrolidone in a ratio of 3:1 showed the most appropriate physicomechanical characters with confirmed physical and chemical drug-polymer compatibility. In addition, the in-vitro experiment showed enhanced atorvastatin release over 24 hr. The pharmacological evaluation of F2 formula indicated a significant hypolibedimic effect compared to orally administered atorvastatin. The results revealed that, atorvastatin transdermal patch could be considered as promising drug delivery system for hyperlipidemic patients.