Definitive treatments for primary brain tumours are still sought. Slow-release local chemotherapy may provide a good effect and poly (lactide-co-glycolide) (PLGA) microcylinders could allow this. We evaluated the neurological and histopathological consequences, and MRI visibility, of PLGA microcylinders conjugated with temozolomide and gadolinium implanted in normal canine brains. Eight purpose-bred beagles had cerebral implantation of microcylinders combined with temozolomide and gadolinium. MRI was performed following implantation and 28d later prior to necropsy and brain histopathology. All adverse events were associated with implantation and resolved. Dogs with six microcylinders at 0 and 6.25% gadolinium had mild inflammation and all other dogs had greater brain inflammation, which increased with higher gadolinium concentrations and microcylinder number. Microcylinders with gadolinium were identifiable on MRI. Brain implantation of PLGA microcylinders conjugated with gadolinium and temozolomide is tolerated in healthy beagles. The lowest gadolinium percentage and microcylinder number should be used if this therapy is pursued.