We measured the changes of oxy-hemoglobin (Δ[HbO2]) and deoxy-hemoglobin concentration (Δ[Hb]) in rat breast 13762NF tumors with respect to oxygen or carbogen inhalation using near-infrared spectroscopy (NIRS). The changes in tumor blood flow can be estimated from the NIRS data provided with certain model assumptions. In the theoretical approach, we modified the Windkessel model so as to associate the mathematical model with such physiological parameters of tumor vasculature as total hemoglobin concentration ([HbT]), tumor blood flow (TBF), and tumor metabolic rate of oxygen (TMRO2). The computational results show that hyperoxic gas administration to the rat tumors always gave rise to improvement of tumor Δ[HbO2], while the same hyperoxic gas intervention could result in different responses in tumor [HbT], TBF, and TMRO2. This preliminary study has demonstrated that NIRS, a noninvasive tool to monitor tumor oxygenation, may also be used to estimate tumor perfusion and oxygen consumption rate in response to therapeutic interventions, if a suitable mathematical model is provided.