Now a day an attempt had been made for treatment of drug effectively employed if drug intercalating in microsphere as a sustain release drug delivery systems by micro-technology. Aceclofenac, chemically phenyl acetic acid derivative, effective anti-inflammatory and analgesic drug used in treatment of pain, fever and inflammation in rheumatoid arthritis, ankylosing spondylitis and osteoarthritis and diarrhoea, dyspepsia, abdominal pain, nausea, indigestion, pancreatitis, constipation the most common side effects. So the aim of the present research work was to develop ethyl cellulose microspheres of aceclofenac by oilin- water (o/w) emulsion solvent diffusion evaporation technique and investigated the effect of internal phase volume (IPV), poly vinyl alcohol (PVA) concentration and external phase volume (EPV) formulation variables and revolution per minute (RPM) process variables on percent yield, size, percent entrapment efficiency and percent in vitro drug release profile of aceclofenac microsphere formulations. The size of microspheres formulations were obtained in range of 5±1.3 to 51±2.7 μm, percent yield 75.32±2.21 to 97.87±1.43% and percent drug entrapment efficiency 55.87±2.03 to 89.53±0.93%. Microspheres also investigated for in vitro drug release profile and observed t50 and t70 value in the range of 2.5-10 hrs and 4-12 hrs respectively. Finally concluded, that process and formulation variables play a significant role in particle size and ultimately affect in vitro drug release study.