The S1P3 receptor belongs to the family of G protein coupled receptors which were demonstrated to have regulatory functions in all systems of the body including the immune, cardiovascular and central nervous system. In this work, the role of S1P3 was characterized in neuro-inflammation in regard to its potential role in the neurodegenerative disease multiple sclerosis. It is shown that the SphK1/S1P3 axis is important in astrocyte signalling and probably involved in their activation in vitro. The work further shows that S1P3 is expressed on reactive astrocyte in MS lesions, but not in the mouse brain during neuro-inflammation. In an EAE study, an animal model used to investigate aspects of the human disease multiple sclerosis, it is demonstrated that S1P3 plays no major role in EAE. The therapeutic relevance of these findings remains open, as S1P3 seems to be able to mediate both deleterious and beneficial effects on astrocytes in MS.