Objective To explore the effects of trimetazidine (TMZ) on newly onset of type 2 diabetes mellitus(T2DM) in coronary artery disease patients. Methods Using nested-case-control study and a total of 639 coronary artery patients but without T2DM were enrolled. All the patients were followed-up until March, 2015. T2DM was diagnosed with OGTT. The effects of TMZ on T2DM onset, serum levels of fatty acid, HbA1c and insulin were analyzed. Results At the end of the followed-up, a total of 103 T2DM patients were identified. TMZ is still an independent risk factor of newly onset of T2DM after confounding factors were adjusted. TMZ therapy reduced serum HbA1c, FFA and insulin levels. Besides, TMZ treatment was related to proper time to reach the peak of insulin secretion. Conclusion TMZ therapy can reduce newly onset of T2DM in coronary artery disease patients. The affects of lowering serum FFA, which caused insulin resistance, may be its underlying mechanism.