Ranolazine (RZ) is an antiischemic/antianginal agent employed in therapy of cardiovascular diseases such as myocardial infarction, variant and exercise-induced angina and arrhythmias constipation, headache, nausea and dizziness are the most common side effects. So the aim of the present research work was to formulation characterization and invivo antiischemic activity of RZ loaded ethyl cellulose microspheres in albino wistar rats. RZ microspheres were developed by oil-in-water (o/w) emulsion solvent diffusion evaporation technique with different ratio of drug and ethyl cellulose as a polymer in order to achieve high entrapment efficiency and prolonged release characteristics. The prepared microspheres were subjected for characterization by scanning electron microscopy (SEM), percent yield, Fourier transformer infra red spectroscopy (FTIR), X-ray diffraction (XRD), percent entrapment efficiency and percent drug release. The size of microspheres formulations (F1 to F6) were in range of 20±1.2 to 54±1.7μm, percent yield 78.21±2.31 to 94.24±1.21%, percent drug entrapment efficiency 53.25±0.65 to 85.76±0.78% and percent drug release 56.87 ± 0.34 to 92.74 ± 0.83 % up to 12 hrs. XRD and IR studies showed no interaction between drug and polymer; no degradation during microspheres preparation and stable at storage conditions. Then compare in-vivo activity of optimized F2 microspheres formulation to standard drug in 120-200g of Albino wistar rats of either sex. The results of present study reflect that successfully prepared free flowing RZ loaded EC microspheres and showed a significant reduction in level of cardiac biomarker LDH and CK-MB enzyme for prolong period of time with respect to standard in isoproterenol induced myocardiac infraction (MI) rats.