Core-shell polymer microspheres with poly(d,l-lactic-co-glycolic acid) core and poly(l-lactic acid) (PLLA) shell are developed for the long-term subconjunctival release of brimonidine tartrate (BT) in order to reduce intraocular pressure (IOP) in the treatment of glaucoma. The PLLA-rich shell acts as a diffusion barrier, enabling linear release of BT over an extended period of 40 d. The microspheres are encased in a porous non-degradable methacrylate-based carrier for ease of subconjunctival implantation in a glaucoma-induced rabbit model. In vivo release of BT from the microspheres/carrier system has enabled a significant, immediate IOP reduction of 20 mmHg, which is sustained for 55 d. Long-term IOP reduction may be maintained by periodic replacement of the microspheres/carrier system.