A new polymerizable superoxide dismutase (SOD) mimetic metalloporphyrin macromer was synthesized to minimize inflammatory damage associated with tissue transplantation and biomaterial implantation, such as the use of encapsulated pancreatic islets for the treatment of type I diabetes mellitus (TIDM). This functional SOD mimetic, Mn(III) Tetrakis[1-(3-acryloxy-propyl)-4-pyridyl] porphyrin (MnTPPyP-Acryl), was copolymerized and crosslinked with poly(ethylene glycol) diacrylate (PEGDA) to form hydrogel networks that may actively reduce reactive oxygen species (ROS) damage associated with biomaterial implantation. Solution phase activity assays with MnTPPyP-Acryl macromers showed comparable SOD activity to MnTMPyP, a non-polymerizable commercially available SOD mimetic. This work also describes the development of a new, simple, and inexpensive solid phase assay system that was developed to assess the activity of MnTPPyP-Acryl macromers polymerized within PEGDA hydrogels, which has the potential to fulfill an existing void with the biochemical tools available for testing other immobilized ROS antagonists. With this new assay system, hydrogels containing up to 0.25 mol% MnTPPyP-Acryl showed significantly higher levels of SOD activity, whereas control hydrogels polymerized with inactive MnTPPyP-Acryl macromers showed only background levels of activity. The potential for repeated use of such hydrogel devices to consistently reduce superoxide anion concentrations was demonstrated upon retention of 100% SOD activity for at least 72 h post-polymerization. These results demonstrate the potential that polymerizable SOD mimetics may have for integration into medical devices for the minimization of inflammatory damage upon transplantation, such as during the delivery of encapsulated pancreatic islets.