Objective · To explore the relationship between serum interleukin-6 (IL-6) level and depressive symptoms in schizophrenia. Methods · A total of 239 patients with schizophrenia treated with olanzapine alone for more than 2 years were enrolled. Calgary Depression Scale for Schizophrenia (CDSS) was used to evaluate the depression level of the patients, and they were divided into depression group and non-depression group. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of patients. Serum IL-6 levels were measured by enzyme linked immunosorbent assay (ELISA), and the differences between the two groups were compared. Pearson correlation analysis was used to analyze the relationship between serum IL-6 level and CDSS score. Results · According to the results of CDSS, the patients were divided into depression group (119 cases) and non-depression group (120 cases). Compared with the non-depression group, the PANSS negative symptom subscale score and serum IL-6 level of patients in the depression group were higher (P=0.028, P=0.000). Pearson correlation analysis showed that serum IL-6 level was positively correlated with CDSS score in the depression group patients (r=0.42, P=0.000). Conclusion · The increase of serum IL-6 level may be related to the occurrence of schizophrenia with depression symptoms.