Liver cirrhosis may occur in chronic hepatitis B surface antigen (HBsAg) carriers. Diabetes mellitus (DM)-associated chronic hepatitis may also occasionally lead to cirrhosis; however, its role in the course of chronic HBsAg carriers has not been studied. A cohort of 500 HBsAg carriers (398 men; mean age at entry, 42 +/- 15 years) were followed up longitudinally. After a mean follow-up of 5.8 +/- 3.3 years, 71 (14.2%: 70 men) patients developed cirrhosis. Increased risks of cirrhosis were found among men and the elderly (p < 0.001). Fifteen (21.1%) cirrhotic patients were noted to have had DM for 2-15 years before the development of cirrhosis. By contrast, only eight (1.9%; p < 0.001 ) of the patients without cirrhosis developed DM. When cirrhotic patients were compared to 102 age- and sex-matched non-cirrhotic controls, DM and elevation of serum alanine transaminase levels were found to be independent factors associated with the advent of cirrhosis in multivariate analysis. Other factors, including acute exacerbation, bridging hepatic necrosis, and superinfection by hepatitis C or D viruses, were insignificant. Our results suggest that DM may play a role in the progression to liver cirrhosis in chronic HBsAg carriers. High-risk subjects should be closely monitored for late complications.