Background: Prior studies examining the relation between diabetes mellitus (DM) and prostate cancer risk have reported controversial findings. We examined this association by conducting a detailed meta-analysis of the peer-reviewed literature. Methods: A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to November, 2012 was performed. Methodological quality assessment of the trials was based on the Newcastle-Ottawa Scaleq and the meta-analysis was performed using STATA 12.0. Dose-response regression was conducted with SPSS 19.0. Results: We included 29 studies in the meta-analysis (13 case-control studies, 16 cohort studies), and found an inverse association between DM and prostate cancer (relative risk (RR) 0.84, 95% confidence interval (CI), 0.78-0.91). An inverse association was also observed in non-Asian populations (RR 0.81, 95% CI 0.76-0.87) and population-based studies (RR 0.80, 95% CI 0.77-0.91). No statistical significance was found of the association between prostate cancer risk and the duration of DM (p=0.338), and risk seemed not related with the age of DM diagnosis. Conclusions: This study suggested an inverse relationship between DM and prostate cancer, but without links to duration of disease or age of diagnosis.