The current study represents the latest and new advances in the investigations and applications of the pullulan the wonderful biomaterial which is produced from microbes (generally Aureobasidium sps.) and its derivatives for its applications in the development of various therapeutic formulations. Basically pullulan is an exo-polysacharides which is non-carcinogenic, non-immunogenic and non-mutagenic without having any types of toxicological activities. Similar to dextran and other biopolymer it can be used as a plasma expander. The model drug for this studies i.e Naproxen was used which is one of the most potent non-steroid and anti-inflammatory drug for the treatment of various bone related diseases.In our study we have prepared pH sensitive naproxen-pullulan delivery system in which Pullulan acetate was synthesized by treating 2.5 gm of crude pullulan with 25 ml of formamide at 50°C. For the loading of drug 50 mg of Pullulan acetate was dissolved 5 ml of dichloromethane and to it 80 mg of Naproxen was added. The drug loading efficiency of the prepared microparticle was found to be 80%. The microsphere was also showing a pH sensitive swelling behaviour in Phosphate Buffer Saline (PBS) buffer. The release profile of the drug loaded microsphere reveals that pH of the medium was influencing it at in vitro condition. Moreover the released amount of drug from the pullulan based microsphere at pH 7.2 was 75 times more than that at the pH 1.2. Therefore Pullulan acetate loaded with Naproxen is a useful polymerised materials for the development and formulation of pH sensitive drug. The current study represents the latest and new advances in the investigations and applications of the pullulan the wonderful biomaterial which is produced from microbes (generally Aureobasidium sps.) and its derivatives for its applications in the development of various therapeutic formulations. Basically pullulan is an exo-polysacharides which is non-carcinogenic, non-immunogenic and non-mutagenic without having any types of toxicological activities. Similar to dextran and other biopolymer it can be used as a plasma expander. The model drug for this studies i.e Naproxen was used which is one of the most potent non-steroid and anti-inflammatory drug for the treatment of various bone related diseases. In our study we have prepared pH sensitive naproxen-pullulan delivery system in which Pullulan acetate was synthesized by treating 2.5 gm of crude pullulan with 25 ml of formamide at 50°C. For the loading of drug 50 mg of Pullulan acetate was dissolved 5 ml of dichloromethane and to it 80 mg of Naproxen was added. The drug loading efficiency of the prepared microparticle was found to be 80%. The microsphere was also showing a pH sensitive swelling behaviour in Phosphate Buffer Saline (PBS) buffer. The release profile of the drug loaded microsphere reveals that pH of the medium was influencing it at in vitro condition. Moreover the released amount of drug from the pullulan based microsphere at pH 7.2 was 75 times more than that at the pH 1.2. Therefore Pullulan acetate loaded with Naproxen is a useful polymerised materials for the development and formulation of pH sensitive drug. © 2012 IJDDR, Vuppu Suneetha et al.