Development of a simple, rapid and routine assay of Pioglitazone Hydrochloride (PHCl) for the investigation of its pharmacokinetic parameters in human plasma and bioequivalence study of 45mg PHCl tablets manufactured locally (Test) and originally (Reference). After extraction of PHCl from plasma, it was chromatographed with mobile phase consisting of phosphate buffer: acetonitrile: methanol (65:25:10) at flow rate of 2ml/min and detected at wavelength of 235nm. The pharmacokinetic study was conducted in a 2 X 2 crossover design involving 24 volunteers. The criteria used to assess bioequivalence of the two products were AUC(0-24), AUC(0-∞),Cmax, and tmax. The described method for analysis showed that the recovery of PHCl from plasma was 99.84%, the limit of detection was 0.05μg/ml and the regression analysis for the drug concentrations indicated excellent linearity(r > 0.999). Statistical analysis (ANOVA) of the measured parameters showed that there was no significant difference between the two products. The HPLC method presented is direct, simple, reproducible, sensitive and linear for the determination of PHCl in human plasma & is adequate for its clinical pharmacokinetic studies, besides, the Test was found to be bioequivalent to the Reference and both products can be considered interchangeable in medical practice.