Mucoadhesive microspheres of sitagliptin (SITCM), a new anti-diabetic drug was prepared with carbopol 934 P using Buchi B-90 nano spray drier and optimized to analyse the key effects and relations of three factors on formulation of SITCM were studied. The appearance of the microspheres was found to be shriveled to nearly spherical, with a narrow size of 2-8 mu m. The drug loading and percentage yield was found to be 73 +/- 0.2% and 92 +/- 0.3%, respectively. In vitro release indicated Korsmeyer-Peppas pattern mucoadhesion of SITCM-8 was found to be 7.8 +/- 0.3 h. In vivo studies in rats suggest that the sitagliptin was retained in the gastrointestinal tract for an extended period of time (similar to 12 h) and control group was reduced significantly (similar to 4 h). This study concludes that the mucoadhesive microsphere could be one of the most appropriate drug delivery approaches for the successful delivery of sitagliptin.