Ishcemia initially induces reversible metabolic, mechanical and electrocardiographic (ECG) changes in the heart. Metabolic changes in the ischemic myocardium arise from the decrease in glucose oxidation. Pharmacological manipulation of cellular energy metabolism, appears to be a rational approach and Trimetazidine (TMZ) is a representative of a new class of metabolic agents with a myocardial anti-ischemic effect achieved independently of changes in the oxygen supply to demand ratio. Diabetic patients may gain a specific benefit as metabolic alterations consequent to DM are closely linked to the accumulation of various acyl carnitine and co-enzyme derivatives. The purpose of the present study is to determine the effect of TMZ on cardiac function in diabetic patients with IHD. To achieve this purpose we studied 21 diabetic patients (pts) with ischemic cardiomyopathy (CM) (19 M, 2 F mean age 57.5+4.2). IHD was diagnosed by clinical history in all pts, coronary angiography in 5 pts, history of CABG in 1 pt & echocardiographic evidence of regional wall motion abnormalities in all pts. Ten pts received TMZ (9 M, 1 F, mean age 56+7.2) whereas a control group of 11 pts (10 M, 1 F, mean age 59.4+8.9) received only conventional treatment without TMZ. Following clinical evaluation, all pts were subjected to resting ECG & 2D echocardiography. TMZ was received at a dose of 20 mg tid, by group 1 pts. Low dose dobutamine stress echocardiography (DSE) was performed on admission & after 60 days in both groups. DSE was done under continuous ECG monitoring, dobutmaine was infused at an incremental regimen of 5 mic/Kg/min every 3 minutes until a maximum dose of 20 mic/Kg/min. Beside measurements of HR & BP., Echo parameters as LVEDD, LVESD, FS% EF%, regional wall motion score index (RWMIS) were taken at rest & after DSE, both before & after 60 days of TMZ treatment.Compared to control group; TMZ group showed a significantly greater improvement in the FS% (19.0+2.7 to 22.6+3.6 vs 18.9+3.4 to 19.4+2.9; P value < 0.01) and EF% (38.7+4.9 to 45+6.4 vs 38.5+5.7 to 39.0+4.3, P value < 0.01), with significantly greater reduction of RWSI (1.9+0.4 to 1.6+0.3 vs 1.9+0.4 to 2.1+0.2, P value< 0.01). Following DSE, echo parameters again exhibited a significant improvement. Thus compared to measurements before therapy, TMZ shows significantly greater increase FS% (24.1+4.2 to 26.8+4.1 vs 20.9+4.2 to 22.8+2.7, P value: 0.019) & EF% (47.5+7.1 to 52.1+7.1 vs 40.5+7.6 to 42.9+6.1; P value: 0.014), with significant reduction of RWSI (1.7+0.3 to 1.4+0.2 vs 1.8+0.3 to 1.7+0.4, P value< 0.01). Thus compared to control group TMZ treated group exhibited significantly % improvement in terms FS% (19% vs 2%, P value< 0.01), EF% (16.2% vs 1.2%, P value< 0.01). & RWSI (15.7% vs 9.5%, P value< 0.01).Conclusion: Significant improvement in LV systolic function was shown at rest and by DSE following treatment by TMZ. Through inhibiting fatty acid oxidation and enhancing normal metabolic pathway, TMZ seems to be of particular benefit in that subset of IHD who have concomitant DM with its adverse effects on cardiac metabolism. TMZ may serve as an adjuvant treatment for diabetic pts with IHD to halt the deterioration in the LV systolic function.