This study aimed to develop a rapid, user-friendly, economic and sensitive method for analyzing imatinib mesylate (IMA) and erlotinib hydrocloride (ERLO) in mice plasma using ultrahigh performance liquid chromatography (UPLC). Separation was achieved by isocratic elution using a mobile phase consisting of the mixture of 3mM triethylamine and acetonitrile with the ratio of 60:40 using XTerra (R) RP8 column (5 mu m 4.6x150 mm). The retention time for IMA was 4.9 minutes with a flow rate of 1.5mL/min, while the retention time for ERLO was 5.0 minutes with a flow rate of 0.8mL/min. Injection volume was set to 20 mu L and the detector wavelength was 320 nm. Detection limits for imatinib mesylate and erlotinib hydrochloride were 95 and 72 ng/mL, respectively. This method was validated in terms of linearity, selectivity, recovery, precision and accuracy. This simple and sensitive method can be successfully used in research and easily adapted for analyses of other types of tyrosine kinases receptor inhibitors.