Objective: To determine the effect of trimetazidine on cardiac function and exercise tolerance in primary hypertension patients with type 2 diabetic. Methods: In this randomized, double-blind, placebo-controlled prospective study, 60 primary hypertensive patients with diabetic were equally assigned into two groups, patients received trimetazidine (20 mg, 3 times a day) or placebo for 1 year. Echocardiography, cardiopulmonary exercise testing were performed; and the plasma N terminal pro B type natriuretic peptide (NT-ProBNP), hr-CRP, TNF-α, angiotensin Ⅱ and endothelin concentration were determined before and after treatment. Results: In trimetazidine group, the left ventricular mass index, the mitral flow velocity E wave to A wave ratio (E/A), the peak early diastolic velocity (V_E) to late diastolic velocity (V_A) ratio (V_E/V_A) and the peak systolic velocity (Vs) were significantly improved, the plasma NT-ProBNP level was significantly decreased, and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were significantly increased (all P < 0.05); plasma concentration of hr-CRP, TNF-α, angiotensin Ⅱ and endothelin were significantly reduced after trimetazidine treatment, compared with baseline (all P < 0.05) and with placebo (all P < 0.05). There were no significant differences in any of above parameters after treatment in placebo group (all P>0.05). No severe adverse reaction was observed in both groups. Conclusion: For patients with both hypertension and diabetes, trimetazidine can improve cardiac function and increase exercise tolerance.