Objective To explore the mechanism of chronic pelvic pain syndrome(CPPS) using fMRI based on regional homogeneity (ReHo) method. Methods 19 male patients with CPPS and 19 age-matched male healthy controls were enrolled in this study. Resting-state fMRI data were obtained from all participants using a 3.0 T magnetic resonance unit. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score and pain subscale were obtained from each participant before the magnetic resonance imaging scan. The softwares of SPM5 and DPARS were adopted to process the resting-state fMRI data and acquire individual ReHo maps for each participant. A two-sample t-test was used to detect the differences of cerebral regions in the ReHo maps between the patients with CPPS and the healthy controls. AlphaSim based on Monte Carlo simulation was applied for multiple comparison correction. After correction, P<0.05 was considered statistically significant. The time series in the significantly alerted cerebral regions of the patients were extracted and correlated with the NIH-CPSI pain subscales. Results The patients with CPPS had significantly decreased ReHo in the left anterior cingulate cortex (MNI coordinate: -5, 31, 26) and the right anterior cingulate cortex (6, 12, 28) (P<0.05, Alphasim correction), while significantly increased ReHo in the right thalamus (9, -10, 7) compared with the healthy controls (P<0.05, Alphasim correction). In the patients with CPPS, there were significantly negative correlations between the left anterior cingulate cortex and the NIH-CPSI pain subscale (r=-0.6, P<0.05), and between the right anterior cingulate cortex and the NIH-CPSI pain subscale(r=-0.5, P<0.05), while a significantly positive correlation between the right thalamus and the NIH-CPSI pain subscale (r=0.6, P<0.05). Conclusions The patients with CPPS have alerted cerebral regions compared with the healthy controls. The abnormal brain regions maybe result in dysfunction pain modulation in patients with CPPS. Key words: Regional homogeneity; Resting-state; fMRI; Chronic pelvic pain syndrome