To investigate whether increased dipeptidyl peptidase 4 (DPP4) activity predicts new-onset hypertension in Chinese patients. A prospective study was conducted for 1884 adults (804 men/1080 women) aged 18-70 years without hypertension. Participants were examined in 2007 (baseline) and 2011 (follow-up) and circulating DPP4 activity, mannose 6-phosphate receptor (M6P-R) concentration, inflammatory markers and oxidative stress parameters were measured. After a 4-year follow-up, 296 individuals developed hypertension with an incidence of 39 per 1000 patient years. In multiple linear regression analyses, baseline DPP4 activity was an independent predictor of an increase in M6P-R, inflammatory markers and oxidative stress parameters over a 4-year period (all P < 0.01). Cox proportional hazards models revealed that DPP4 activity independently predicted the risk of developing hypertension (relative risk 2.68 (95% confidence interval 1.71-4.21) P < 0.01). Our results indicate that DPP4 activity is an important predictor of hypertension onset in apparently healthy Chinese individuals. This finding may have important implications for understanding the effects of DPP4 in promoting inflammation and oxidative stress in the pathogenesis of hypertension.