Four methods were developed for simultaneous determination of sulfaquinoxaline-Na and pyrimethamine in their combined pharmaceutical formulations. The first one was a densitometric method where chloroform-methanol (9: 1, v/v) was the developing system and the plates were scanned at 254 nm. The obtained spots appeared at Rf 0.64 and 0.35 and determined in the range of 0.5-10.0 μg/spot and 0.1-10.0 μg/spot for sulfaquinoxaline-Na and pyrimethamine, respectively. Furthermore, three spectrophotometric methods manipulating ratio spectra namely, ratio difference method, extended ratio subtraction method coupled with ratio subtraction method and mean centering method were established for the determination of the two studied drugs in the presence of propylene glycol as a solvent. Linear correlation was found over the concentration range of 2-25 μg mL-1 and 3-15 μg mL-1 for the two drugs, respectively. The proposed methods were successfully applied for analyzing the cited drugs in their veterinary pharmaceutical formulations. The obtained results were statistically analyzed and found to be in accordance with those given by a reported method. The validity of the methods was evaluated according to ICH guidelines.