The aim of this study was to formulate and evaluate mucoadhesive sodium alginate microspheres for nasal administration of Pentoxifylline to avoid first-pass metabolism. Microspheres were prepared using an ionic gelation process using a 2³-factorial design. We investigated the effects of several factors on particle size and in vitro mucoadhesion, including drug-to-polymer weight ratio, calcium chloride (CaCl₂) concentration, and cross-linking time. Particle size of the mucoadhesive microsphre was found in the 27.01 to 33.78 µm range, were the in-vitro mucoadhesive result showed in the range 76.14 to 87.58 %. The microspheres were characterized by SEM to study the shape and distribution of drugs within the microspheres. The surface morphology studied by SEM showed spherical shape and smooth surface of pentoxifylline sodium alginate loaded microsphere containing 2% w/v of Carbopol prepared by ionotropic gelation method. F6 formulation shows highest percentage of in-vitro diffusion 84.78 %. In vitro dissolution tests were performed in pH 6.2 phosphate buffer indicated non- Fickenian type of transport for the diffusion of drug from the Pentoxyfylline mucoadhesive microsphere. It has been shown that the Hixson-Crowell model best describes the release of Pentoxyfylline from Carbopol. The F6 formulation utilized use of the Hixson-Crowell diffusion model of drug release, which was determined to be the model that best fit the data (r²=0.9697). The formulation showed that the Fickian mechanism of drug release was acting when the n value was less than 0.5.