As the bioconversion of cellulosic substrate to fuels is essential to suppress the dependence on conventional fossil fuels, development of new improved bioprocess engineering techniques are requisite for fulfilling the rising demand of biofuels throughout the world. For this purpose, the effect of particle size on enzymatic hydrolysis of cotton cellulose has been explored in great detail. The model simulations for the enzymatic hydrolysis of microcrystalline cotton cellulose of different concentrations (0.25-20 mg/ml) were performed for the average particle size ranging from 0.78 to 25.52 μm. A highest glucose yield (99.8%) was observed for the smallest particle size of 0.78 μm in 50 h of enzymatic hydrolysis. Effect of inhibition (competitive and non-competitive) on glucose yield was analyzed through the incorporation of product inhibition in the kinetic model. The extent of cleaving of 1-4 glycosidic bonds by cellulase was quantified by degree of polymerization (DP) of cotton polymers which also indicates that faster scission of bonds can be observed under competitive inhibition and, hence, more glucose yield. The model simulations shows that particle size reduction may be useful for reducing the long residence time required for the hydrolysis step in the bioconversion of cellulose to ethanol.