Trolamine salicylate (TS) is a topical anti-inflammatory analgesic used to treat small joint pain. The topical route is preferred over the oral one owing to gastrointestinal side effects. In this study, a poly(lactide- co-glycolide) (PLGA)-based in situ bio-adhesive film-forming system for the transdermal delivery of TS was designed and evaluated. Therefore, varying amounts (0%, 5%, 10%, 20%, and 25% ( w/ w)) of PLGA (EXPANSORB ® DLG 50-2A, 50-5A, 50-8A, and 75-5A), ethyl 2-cyanoacrylate, poly (ethylene glycol) 400, and 1% of TS were dissolved together in acetone to form the bio-adhesive polymeric solution. In vitro drug permeation studies were performed on a vertical Franz diffusion cell and dermatomed porcine ear skin to evaluate the distinct formulations. The bio-adhesive polymeric solutions were prepared successfully and formed a thin film upon application in situ. A significantly higher amount of TS was delivered from a formulation containing 20% PLGA (45 ± 4 µg/cm 2) and compared to PLGA-free counterpart (0.6 ± 0.2 µg/cm 2). Furthermore, the addition of PLGA to the polymer film facilitated an early onset of TS delivery across dermatomed porcine skin. The optimized formulation also enhanced the delivery of TS into and across the skin.