The purpose of the present work, which is focused on the loading of bromocryptine mesylate into biodegradable microspheres with the purpose of prolonging its therapeutic activity, is to study the biodegradation and tissue response after brain and hypophysis tissue implantation. For this purpose, surgery was performed under aseptic conditions. Sprague-Dawley rats were divided into three groups. The rats were anaesthetised with intraperitoneal injections of a ketamine hydrochloride (Ketalar)/xylazine hydrochloride (Romphun) mixture. They received Either blank poly(L-lactides), poly(D,L-lactides) and poly(D, L-lactidc-co-glycolide) microspheres or bromocryptine mesylate-loaded microspheres ill the brain and hypophysis tissue by intracerebral implication, The right hemisphere was used as a control and the left hemisphere was used as a sample. The rats were sacrificed with all overdose of anaesthetic at 7 days, 14 days and 4 months after the implantation. Histological examinations were performed with light microscopy and transmission electron microscopy. Blank microspheres showed no inflammatory response or other adverse effects in the rat brain and hypophysis and completely biodegraded after 4 months in vivo. No physical signs of toxicity toxicity were shown by the animals receiving bromocryptine mesylate-loaded microspheres. The cellular response was characterized by the presence of fibroblast at day 7. At day 120, the cell reaction was the same as that at day 21. This work: suggests that bromocryptine mesylate-loaded biodegradable microspheres is possibly safe to implant in the mt brain and hypophysis, and that these I,microspheres carl be used in prolonging bromocryptine mesylate release.