AbstractChronic electrodes are widely used for brain degenerative and psychiatric daises such as Parkinson's diseases, major depression, and obsessive‐compulsive disorder, and for neuronal prosthesis. Brain immune reaction to electrodes in the form of glial scar encapsulates the electrode and reduces the efficacy of deep brain stimulation and neuronal prosthesis. State‐of‐the‐art strategies for improving brain–electrode interface use passive protein coating to “camouflage” the electrode from the immune system. In this study, we actively reduced the brain immune reaction to the chronic electrodes using immune suppressing protein, that is, interleukin (IL)‐1 receptor antagonist. IL‐1 receptor antagonist‐coated electrodes and noncoated electrodes were chronically implanted in rats. An additional group of rats was chronically implanted with IL‐1 receptor antagonist‐ and laminin‐coated electrodes (as passive protein). Examination of glial scaring 1ne and 4 weeks after implantation indicated a significant reduction in the amount of glial scar in the vicinity of the IL‐1 receptor antagonist‐coated electrode in comparison to both noncoated electrode and laminin‐coated electrodes. The results strongly suggest that active immune suppressing protein reduces the level of immune reaction to chronic electrodes already after 1 week after implantation and generates less immune reaction then passive protein coating. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.