Hepatitis C virus (HCV) infection may contribute to the development of type 2 diabetes mellitus. However, this association at the population level remains unclear. The aim of this pilot study is to examine the relationship between HCV infection and the development of type 2 diabetes mellitus in an HCV hyperendemic area where we conducted health screenings in 1995. After 7 years of follow-up, we evaluated the relative risk of the development of type 2 diabetes mellitus in anti-HCV-inhabitants. Among 71 subjects free of diabetes mellitus in 1995, 7 developed type 2 diabetes mellitus during the 7-year follow-up evaluation. Overall, anti-HCV-positive subjects were nearly 3-fold as likely as anti-HCV-negative subjects to develop diabetes mellitus, but this difference was not statistically significant (p=0.08). After stratification of the anti-HCV-positive group according to serum HCV core titer, a significant increase in the incidence of diabetes was seen in subjects with high titer of HCV core compared to anti-HCV-negative subjects (p=0.02; relative hazard, 5.60; 95% confidence interval, 1.41 to 37.42). In conclusion, HCV infection potentially has a significant role in the development of type 2 diabetes mellitus at the population level. Further large-scale studies are needed to confirm these preliminary findings.