Oral therapy of NSAIDs for treatment of rheumatoid arthritis causes gastric irritation and ulceration. In the present study transdermal patch of ketoprofen was developed using hydroxyl propyl methyl cellulose E5 and Eudragit S100. Patches were prepared by solvent evaporation method. Optimization was carried out by 32 factorial design with polymer concentration (HPMC E5) and plasticizer concentration (propylene glycol) as independent variables. Patches were evaluated for folding endurance, surface pH, drug content, percent moisture content, water uptake and swelling studies. Ex vivo permeation studies of optimized patch was performed using Franz diffusion cell while bioadhesion force and tensile strength were measured by using texture analyzer. Hydrophilic nature, swelling ability and wettability of polymer and plasticizer were responsible for increase in flux and bioadhesion with increase in their concentrations in the factorial batches. Swelling index of all formulations was in the range of 17.3 ±1.2 to 65.29 ±4.78 up to 3h. Flux obtained from all batches was in the range of 3.37±0.23 to 5.43±0.13µg/h/cm2. Anti-inflammatory studies using carrageenan-induced rat paw edema showed greater paw swelling reduction in case of ketoprofen patch. Cumulative percent drug permeation of optimized patch through nylon 66, Wistar rat skin and cadaver skin was found to be 92.3% >86.28 %>63.42% in 8h, while flux order was 6.073> 5.442 > 2.219 µg/h/cm2 respectively. The study concludes that transdermal patch of ketoprofen will be more efficacious with absence of gastric irritation observed in oral formulations. Keywords: Ketoprofen, Bioadhesion, HPMC E5, Flux, Backing membrane