The aim of this study was to study the effect of ciprofloxacin (CFX) and ibuprofen (IBF) on the in vitro metabolism of rosiglitazone (RGZ) in human liver microsomes and on the pharmacokinetics of RGZ in healthy human volunteers. A randomized, placebo controlled, 3-way crossover design oral pharmacokinetic study was done in healthy human male volunteers and in vitro metabolism studies were done in human liver microsomes to study the effect of CFX and IBF on RGZ metabolism. Each subject received orally either 8 mg of RGZ with a placebo or co-administration with either 500 mg of CFX or 400 mg of IBF. Plasma concentrations of RGZ were estimated using a validated LC-MS/MS method and the metabolism studies samples were analyzed by a reported HPLC method. There was no statistically significant difference observed in the pharmacokinetic parameters viz., AUC(0-t), AUC(O-infinity), Cmax, Tmax, Kel and t1/2 of RGZ following co-administration of either CFX or IBF. Both CFX and IBF did not affect the in vitro metabolism of RGZ in human liver microsomes.