KATP channel openers (KCOs) are useful for the prophylactic and/or therapeutic treatment of CNS chronic inflammation associated with a disease or state in a mammal, including a human. The administration of KCOs, including the groups of benzopirans, cyanoguanidines, thioformamides, benzothiadiazines, pyridyl nitrates, pyrimidine sulfates, cyclobutenediones, DHP-related compounds, tertiary carbinols, 6-sulfonil-chromenes, 1,2,3-triazoles, pyridothiadiazines, benzothiazines, halogenquinazolins and phenylbenzimidazoles, and in particular, the compound diazoxide, result in a reduction of reactive microglial response in various CNS pathologies such as axonal injury, brain tumors, traumatic damage, neurodegeneration, spinal cord injury, infectious and autoimmune diseases. KCOs, isotopically modified, are also useful for the preparation of diagnostic agents for detection and follow-up of CNS chronic inflammation.