Accumulating evidence showed that interleukin-2 (IL-2) may be involved in the pathophysiology of schizophrenia. Increased IL-2 levels have been found in the serum of schizophrenia patients with mixed results. In the present study, we assessed serum IL-2 levels in a large group of 160 schizophrenia patients compared to 60 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum IL-2 levels were measured by sandwich ELISA. The results showed that IL-2 levels were significantly higher in chronic patients with schizophrenia than in healthy control subjects (p<0.001). Correlation analysis revealed a significantly negative association between IL-2 levels and the PANSS cognitive and positive subscales (both p<0.01). Stepwise multiple regression analyses confirmed IL-2 as the influencing factor for the cognitive and positive subscales of the PANSS. Our findings suggested that increased IL-2 may be involved in the cognitive impairments and psychopathology of chronic schizophrenia.