From the past few decades, scientist interest focused in the area of improvement of therapy and development of microspheres by oil-in-water (o/w) emulsion solvent diffusion evaporation technique. Aceclofenac (ACF) is an analgesic and anti-inflammatory and diarrhoea, dyspepsia, abdominal pain, nausea, indigestion, pancreatitis, constipation the most common side effects. So the aim of the present research work was to formulation designing, characterization and in-vivo anti-inflammatory and analgesic activity in rats. ACF loaded EC 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 10±2.1 to 51±2.7 μm, percent yield 75.32±2.21 to 95.43± 1.13%, percent drug entrapment efficiency 55.87±2.03 to 87.53±2.12% and percent drug release 58.36 ± 0.32 to 94.68 ± 0.54 % up to 12 hrs. IR and XRD 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 microspheres formulations to standard drug in 120-200g of Albino wistar rats of either sex. The results of present study reflect that successfully prepared free flowing ACF loaded EC microspheres by o/w emulsion solvent diffusion evaporation technique and significantly reduction in an inflammation observed when it compared to standard ACF and also showed significant analgesic activity in rats.