Angiogenesis is a fundamental process of wound healing, embryogenesis etc. but occurs in cancer and chronic inflammation pathologically. HET-CAM assay is a useful, well established and animal alternative test to screen anti-inflammatory potentials of pharmaceutical products as well as nano-formulations. Dexketoprofen trometamol (DT) belongs to the nonsteroidal anti-inflammatory drug (NSAID) group which is a rapidly acting analgesic ingredient. Because DT has a short half-life, high and frequent dosing is used in treatment. The need of design and producing a new oral prolonged-release dosage form containing DT is the major aim of the study with low dose and low side effects. Chitosan (CS) has been widely used in the pharmaceutical area because of its favorable biological properties. In this study, DT loaded CS nanoparticles (CS-NPs) were produced by spray drying method for oral drug delivery. Structures of CS-NPs were elucidated by particle size, zeta potential, SEM, DSC, FT-IR and H-1 NMR. High encapsulation efficiency was obtained (73-84%) for the prepared formulations. In vitro release was examined in pH 1.2 buffer and pH 6.8 buffer. DT-loaded CS-NPs showed prolonged release, particularly at pH 6.8. Weibull kinetic model was found to fit best to DT release from CS-NPs in both release medium. The anti-inflammatory activity of optimum formulation (M-DT) was examined using the in vivo HET-CAM assay. The anti-inflammatory activity results indicated that M-DT coded NPs formulation showed significantly good anti-inflammatory potential with closer inhibition value to the standard anti-inflammatory DT at one fifth lower dosage. According to the proposed method and results it can be successfully applicable to the NP preparation containing DT and it could be concluded that DT loaded CS-NPs seem to be a promising prolonged release drug delivery system for oral administration with low dose and high efficiency.