Amyotrophic lateral sclerosis (ALS) is a late-onset disease characterized by motor neuron degeneration. Earlier experiments on transgenic mice carrying the human mSOD1 gene presented strong evidence that microglia (MG) significantly contribute to disease progression in the later phase of the disease. Here, we established a novel primary cell culture model of ALS using ex vivo transplants of adult MG. Spinal cord EGFP-labelled MG of clinically affected transgenic SOD1G93A mice or age matched controls were grown on a astrocytes monolayer and MG activation was analysed using the patch-clamp technique, and immunohistochemistry. In addition, ELISA was used to measure the release of relevant inflammatory markers without and under the influence of ATP and ATP-modifying substances, e.g. BBG, TNP-ATP and Clopidogrel (CG). Subsequently, CG was applied orally to SOD1G93A mice and mouse survival was analysed. MG cells from SOD1G93A mice revealed morphological signs of activation compared to controls. Proliferation activity, using WST-1 assay, showed unaltered viability of SOD+ MG. In patch-clamp experiments SOD+ MG showed increased inward and outward currents compared to controls. Supernatants of unstimulated SOD+-and control MG were devoid of measurable amounts of cytokines. LPS induced a release of TNF-, RANTES, IL-6, IL-12, CCL3 and KC, and 50 mM ATP led to a decrease in LPS-induced cytokine release in SOD+ MG and controls. From the used substances, only CG, administered at a concentration of 100 mM in the presence of ATP/LPS, reduced IL-12, MIP-1 and KC release in SOD+ MG. When applied orally. However, CG did not prolong survival of SOD1G93A mice. This novel cell culture model will allow us to analyze adult MG cells of SOD1 mice under naive conditions as well as in response to drug application.