We aimed to quantitatively investigate the alteration of parotid perfusion after irradiation using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on a two-compartment tracer kinetic model. This study enrolled 19 patients (53.2 +/- 14.9 years) treated by head and neck radiotherapy and 19 age-relevant and sex-matched subjects as a control group. Perfusion parameters (K ( el ), k (21) and A) of parotid glands were analyzed based on the Brix model from T1-weighted DCE-MRI. Suitability of the Brix model was evaluated via Monte Carlo simulation for the goodness-of-fit. Analysis of nonlinear goodness-of-fit showed that the Brix model is appropriate in evaluating the parotid perfusion (R(2) = 0.938 +/- 0.050). The irradiated parotid glands showed significantly lower K ( el ) (P < 0.0005) and k (21) (P < 0.05) and consequently significantly higher value of peak enhancement (P < 0.0005) and time-to-peak (P < 0.0005) compared with non-irradiated ones, suggestive of gradual and prolonged accumulation and delayed wash-out of contrast agent due to increased extracellular extravascular space and decreased vascular permeability in the irradiated glands. Linear regression analysis showed dose-dependent perfusion changes of the irradiated parotid glands. We conclude that quantitative DCE-MRI is a potential tool in investigating parotid gland perfusion changes after radiotherapy.