Objective: Our aim was to estimate whether diabetes mellitus (DM) may be associated with an increased risk of colorectal cancer (CRC) mortality in Japan. Methods: The Japan Collaborative Cohort (JACC) Study is a nationwide prospective study, initiated in 1988, which involves 110,585 subjects (age range: from 40 to 79 years; 46,395 males and 64,190 females). Our present analysis population comprised 96,081 (40,510 men and 55,571 women) who provided details on DM history. The questionnaire also included age, sex, weight, height, family history of CRC, smoking, drinking and exercise habits, and education. Cox proportional-hazard regression was used to estimate the hazard ratio (HR). We used SPSS 21 software to analyze all data. Results: Among the participants with DM, we followed up for 71,174 person-years and 640. deaths from CRC were confirmed; and, among the non-diabetic participants, 785 CRC deaths were identified during 1,499,324 person-years. After adjusting for multivariate confounding factors, such as age, sex, body mass index (BMI), family history of colorectal cancer, smoking habit, drinking habit, physical activity (sports and walking) and education, DM was associated with an increased risk of CRC death (HR 1.4, 95% confidence interval [CI] 1.0-2.0). Diabetic women, but not diabetic men, experienced increased mortality from CRC (HR 1.7, 95% CI 1.0-3.0). Conclusion: The risk of CRC mortality is significantly increased in both sexes and women with diabetes, but no significant increase was seen for diabetic men among Japanese.