The nasal bioavailability of fluorescein isothiocyanate-dextran (FITC-dextran) (Mw = 4300) encapsulated in non-mucoadhesive and mucoadhesive microspheres in New Zealand White rabbits was investigated. FITC-dextran was administered nasally encapsulated in carbopol 934P, chitosan and lactose microspheres and the bioavailability compared to intravenous administration of FITC-dextran solution. Administration of FITC-dextran as carbopol microspheres produced a significantly greater bioavailability (33%) than after administration as chitosan (13%) and non-mucoadhesive rapidly dissolving control lactose microspheres (9%). The FITC-dextran terminal plasma half-lives after carbopol 934P and chitosan microsphere administration were significantly longer than after intravenous administration of FITC-dextran. The FITC-dextran terminal plasma half-life after carbopol 934P microspheres administration was significantly longer than after lactose microsphere administration. This data suggested that the increase in FITC-dextran bioavailability after carbopol 934P microspheres administration was due to increased residence at the absorptive site via mucoadhesion and reduced mucociliary clearance. A change in mucosal permeability could not however be discounted especially for the chitosan microspheres.