A novel flow injection-chemiluminescence (FI-CL) approach is proposed for the assay of pioglitazone hydrochloride (PG-HCl) based on its enhancing influence on the tris(2,2'-bipyridyl)ruthenium (II)-silver (III) complex (Ru (bipy)3 2+ -DPA) CL system in sulfuric acid medium. The possible CL reaction mechanism is discussed with CL and UV spectra. The optimum experimental conditions were found as: Ru (bipy)3 2+ , 5.0×10-5 M; H2 SO4 , 1.0×10-3 M; DPA, 1.0×10-4 M; KOH, 1.0×10-3 M; flow rate 4.0 mL min-1 for each flow stream and sample loop volume, 180 μL. The CL intensity of PG-HCl was linear in the range of 1.0×10-3 -5.0 mg L-1 (R2 = 0.9998, n = 10) with limit of detection (LOD, S/N = 3) of 2.2×10-4 mg L-1 , limit of quantification (LOQ, S/N = 10) of 6.7×10-4 mg L-1 , relative standard deviation (RSD) of 1.0-3.3% and sampling rate of 106 h-1 . The methodology was satisfactorily used to quantify PG-HCl in pharmaceutical tablets with recoveries ranging from 93.17 to 102.77 and RSD from 1.9 to 2.8%.