: Aim of this study was formulation matrix tablets of nimesulide with controlled release (CR) and immediately release (IR), and evaluation the influence of many types and concentrations of polymers on their in vitro release properties. Four formulations F1 – F4 were designed by wet granulation using different types and amount of polymers, and one formulation with immediately release. The CR matrix tablets formulations (F1 – F4) were composed of using different polymers such as, hydroxypropyl methylcellulose (HPMC-к100м), hydroxypropyl methylcellulose (HPMC-Е6), hydroxypropyl cellulose high viscosity (HPCh), carboxymethyl cellulose (CMC), ethylcellulose (EC-10 cps), whereas IR tablets formulation (F5) contained sodium lauryl sulfate (SLS), polyvinylpyrrolidone (PVP-к30), microcrystalline cellulose (MCC) and lactose monohydrate. The MCC and PVP-к30 were used in a fixed quantity in all CR formulations. The effect of polymer viscosity and its quantity on nimesulide release from two formulations containing the same polymer was studied. Data drug release in vitro was evaluated in phosphate buffer of pH 7.4 by analytical method. The amount of released nimesulide was calculated by preparing standard series in phosphate medium. In vitro profile release indicated that formulations F1 and F2 controlled the drug release for 18h and 10h respectively. Formulations F3 and F4 released 73.58%, 62.5% of their content during 18h consecutively, thus their effect can last for more than a day. While immediately release formulation F5 released more than 90% of its content within 1h, and more than 75% with 30 minutes. MS Excel was suggested to analyze the dissolution profile data for drug release kinetics such as first order, Zero-order, Higuchi and Korsmeyer–Peppas models. However, formulation (F1) containing (HPMC -к100м) as a matrix former showed drug release as highest correlation coefficient (r2) values obtained when first-order model was applied (r2 = 0.9524). Formulations (F2, F3) containing (HPMC -Е6, HPCh and CMC) and IR formulation F5 showed concentration-independent drug release as highest linearity was observed when zero-order model was applied (r2 = 0.9702 – 0.9773 – 0.8747). Whereas, formulation (F4) containing (HPCh and EC) as a matrix former showed the highest correlation coefficient (r2) values when Korsmeyer-peppas model was applied (R2 = 0.9846). Release mechanism of all formulations was Case II relaxation release. This study performed that cellulosic derivatives polymers can be considered ideal components for controlling immediately release of matrix tablets formulation