Surrounding the cells with a semipermeable polymeric membrane allows transplanting unmatched xenogeneic cells without a risk of their rejection. We prepared and tested several 2-hydroxyethyl methacrylate (HEMA) copolymers with alkyl methacrylates or acrylates to find out which was the most valuable for cell encapsulation. On the basis of optimum physical properties and good results of cytotoxicity tests, HEMA-EMA copolymer was chosen as a suitable candidate for encapsulation and immunoprotection of xenogeneic cells before their grafting into the central nervous system (CNS). To characterize the biocompatibility of p(HEMA-co-EMA) copolymer in the CNS, we implanted microcapsules made of this hydrogel into the brains of adult rats that were allowed to survive for 0.5, 1, 3, 6, and 9 months. Analysis of histological sections containing the implantation site was aimed at assessment of the cellular density at the implant-brain interface and identification of cell types participating in a tissue reaction. Our results indicated that the tissue reaction that was observed was caused largely by the implantation procedure because HLA-DR- and GSI-B4-positive macrophages/microglia infiltrated mainly the implantation channel. The number of these cells declined with time, which was true also for GFAP-positive reactive astrocytes, as well as for foreign body giant cells. The amount of connective tissue components surrounding the implanted microcapsules increased only slightly. These findings indicated that p(HEMA-co-EMA) hydrogel was well tolerated after implantation in the brain.