Morphologic abnormalities of the insular cortex have been described in psychotic disorders such as schizophrenia, but it remains unknown whether these abnormalities develop progressively over the course of the illness. In the current study, longitudinal magnetic resonance imaging data were obtained from 23 patients with first-episode psychosis (FEP), 11 patients with chronic schizophrenia, and 26 healthy controls. The volumes of the short (anterior) and long (posterior) insular cortices were measured on baseline and follow-up (between 1 and 4 years later) scans and were compared across groups. In cross-sectional comparison at baseline, the FEP and chronic schizophrenia patients had significantly smaller short insular cortex than did controls. In longitudinal comparison, the FEP patients showed significant gray matter reduction of the insular cortex over time (-4.3%/2.0 years) compared with controls (0.3%/2.2 years) without significant subregional effects, but there was no difference between chronic schizophrenia patients (-1.7%/2.4 years) and controls. The gray matter loss of the left insular cortex over time in FEP patients was correlated with the severity of positive and negative symptoms at follow-up. These findings indicate that patients with psychotic disorders have smaller gray matter volume of the insular cortex especially for its anterior portion (short insula) at first expression of overt psychosis, but also exhibit a regional progressive pathological process of the insular cortex during the early phase after the onset, which seems to reflect the subsequent symptomatology.