This study aimed to investigate whether elevated inﬂammatory cytokine expression induced white matter integrity changes and cognitive impairments in first-episode schizophrenia patients. 27 first-episode schizophrenia patients and 16 healthy controls who underwent diffusion tensor imaging were enrolled. Tract-based spatial statistics analysis exhibited significantly decreased fractional anisotropy and increased radial diffusivity in widespread white matter tracts in patients. Of these tracts, anterior corona radiata (ACR), superior corona radiata, superior longitudinal fasciculus, the body of the corpus callosum, the splenium of the corpus callosum and fornix showed signiﬁcant correlations with higher inﬂammatory cytokine expression. Moreover, ACR and fornix simultaneously showed reduced white matter integrity related to cognitive impairments in working memory and problem solving. These findings provides more evidence for supporting the role of neuroinﬂammation in the pathophysiology of schizophrenia.