Dexamethasone sodium phosphate is a corticosteroid which is widely used for the treatment of brain oedema associated with brain tumours. Like other corticosteroids, dexamethasone sodium phosphate has many adverse effects which restrict its use at an effective concentration. Dexamethasone sodium phosphate suppresses the immune system and causes neuropathological complications during long-term therapy due to muscle weakness caused by potassium loss. The aim of this study was to minimize these adverse effects and to extend the release time of the active ingredient by preparing microsphere formulations with biodegradable, biocompatible, natural polymer bovine serum albumin (BSA). In order to modify the release time, the amount of cross-linking agent, the time of cross-linking and the amount of dexamethasone sodium phosphate were changed. In vitro release studies were performed and release profiles were determined. The factors affecting the release time, particle size distribution, surface morphology and drug loading ratios of microspheres were investigated. For in vivo studies, an experimental model, the so-called cold lesion method, was used to form oedema in rat brain. Microspheres were implanted and the effectiveness of formulations investigated using the tissue weight method, lipid peroxidation ratio and histological evaluations. As a result, the implantation of BSA microspheres demonstrated no significant advantages when compared to systemic treatment.