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Periventricular leukomalacia (PVL) is a major neuropathologic form of brain injury. It is mostly observed in low-weight preterm infants and frequently causes cerebral palsy. PVL begins as a coagulation necrosis in the white matter around the ventricles and continues with proliferation of astrocyte and macrophage. PVL is known that causes to neuromotor control disorders (spastic diplegia), seizures, visual-speech disorders, cognitive disorders. In this article, we report a case of schizophrenia with periventricular leukomalacia. A 24-year-old female, graduated from secondary school, living with her family, having no work experience was brought to our clinic by her relatives with complaints of delusions of reference and persecution, agitation, hostile attitudes, social isolation, excessive suspiciousness, disorganized behavior, rigor obsessions, damaging goods. The first psychotic symptoms started nine years ago. In medical query, we learned that the patient with premature birth had normal motor development but her learning and cognitive development was poor than peers. Her neurological examination was normal and routine laboratory examination was within normal limits. In the cranial magnetic resonance imaging periventricular leukomalacia was detected. After remission of psychotic symptoms, she was discharged on risperidone and quetiapine. According to theory developed by current neuroanatomical model named as ‘disconnectivity syndrome’, there is aberrant integration of functionally interdependent circuits, particularly involving frontal and other association cortical regions and their interconnections and connections to limbic and other subcortical structures in schizophrenia. It has been estimated that the increased rates of psychosis in some of the white matter diseases (dismyelinating-demyelinating diseases, tumors of the white matter, systemic inşammatory diseases affecting the white matter and corpus callosum abnormalities) have a possible impact on white matter structures in the pathogenesis of schizophrenia and white matter is an attractive candidate as an anatomical substrate for disconnectivity syndrome. There is a reported case of schizophrenia in a teenager with a history of premature birth, germinal matrix hemorrhage and PVL. They assessed in the context of the case that schizophrenia is part of the spectrum of outcome associated with central nervous system damage observed in premature infants and PVL is a likely pathway to abnormal connectivity and risk for schizophrenia with reference to the theory of disconnectivity. Also the studies about cytokines and PVL offer clues that prenatal exposure to infection might affect the developing brain and increase risk for schizophrenia. Intrauterine infection increases the risk of periventricular leukomalacia (PVL) in premature and infants and cytokines have been implicated in this association. Thomas and Huttunen signified that there is conclusive evidence about infection-related proinşammatory interleukins implicated in PVL and diffuse PVL lesions causes to ventricular enlargement, which is probably the most common pathological marker of schizophrenia and also they supported the hypothesis that schizophrenia is predated by PVL. According to our scanning the literature, previously only one case of schizophrenia was reported association with PVL, in our country, there is no similar case report yet.