The intestinal absorption of oral-anti diabetic drugs in type-II Diabetes mellitus is altered when concomitantly administered with other drugs like, antacids, antinuclear drugs, antibiotics and others. A randomized cross over study with two phases and a washout period of 4 weeks was carried out to evaluate the bioavailability of natiglinide with clindamycin.The study has been approved by Institutional ethical committee of Annamalai University. In this study 10 healthy human volunteers received 150mg clindamycin (DALACIN) once daily for 5 days. After and over night fasting on day 6 a single dose of natiglinide 60mg (GLINATE) was given .The blood samples were withdrawn at the following intervals 15, 30, 45, 60,75, 90, minutes 2, 2.5, 3, 4, 5, 7 hours. The plasma samples (20μl) were injected after separation. The mobile phase comprised of acetonitrile300ml with 700 ml mixed phosphate buffer (pH 4.0). Analyses were run at a flow rate of 1.0 ml/min with the UV detector operating at a detection wave length of 210 nm, C18 column (25cm ×4.6mm I’d, 5μm) in HPLC and the pharmacokinetic parameters were calculated by using the software Kineticka. (Version 4.4.1, Innaphase, USA).The study reveals that the plasma concentration of natiglinide significantly increased by the concomitant administration of clindamycin.