In this research work prepared Nimesulide-loaded microsponges (NMRS) gels formulations were demonstrated potential effects in compare to conventional available marketed product in the pain and inflammation treatments. NMRS gels were prepared by using pH independent polymer eudragit RS 100 which is very closely effective in the inhibition of release of drug in conventional manner and increase drug deposition time on the skin surface. During the study the prepared NMRS gel formulations were characterized by using different parameter which was very necessary to make them a novel drug carrier. In this thesis we have described and elaborated all the procedures and protocols for making a novel drug delivery for pain and inflammation disease treatment. In the result, all prepared NMRS gel formulations were clearly increase drug deposition time on the skin up to 24 hour or within the epidermis while minimizing its penetration through the dermis and therefore in to the body. The release pattern of the NMRS gel followed the Korsmeyer’s and Peppas kinetic indicating Fickian diffusion.