Background: 99mTechne um-methoxyisobutylisonitrile (99mTc-MIBI) is one of the substrates for P-glycoprotein (Pgp), which is responsible for resistance to chemotherapy in patients with unresectable lung cancer.Aim of the Study: The aim of this study was to evaluate the performance of 99mTc-MIBI imaging in the assessment of treatment response or resistance in patients with non-small cell lung cancer (NSCLC).Patients and Methods: This study was prospectively conducted on 18 patients with histopathologically proven NSCLC (15 males and 3 females, mean age=57.7±8.1 years). All patients underwent 99mTc-MIBI planar and SPECT as well as CT scan before and a3er 3 cycles of chemotherapy. Region of interests (ROIs) were localized to the tumour mass (T) and over the contralateral normal lung (NL). Early (T/NLe) and Late (T/NLd) uptake ratios were obtained from planar images. The washout rate (T/NLwr) % was also calculated using the formula: [T/NLwr = (T/NLe - T/NLd) / (T/NLe) x 100].Results: According to the response to chemotherapy estimated from follow-up CT, patients were divided into 2 groups; Group 1 included 8 patients showed par al remission (PR) and Group 2 included 10 patients showed no change (NC). (T/NLe) and Late (T/NLd) ratios in PR group (2.1±0.4 and 1.9±0.5, respectively) were significantly higher (p < 0.05) than those in the NC group (1.5±0.3 and 1.4±0.3, respectively) when estimated before starting chemotherapy. On the other hand, these ratios showed no significant statistical difference between the two groups when calculated after treatment. There were no significant differences in the rate of washout between the two groups either before or a3er treatment (p>0.05). The tumor size was significantly lower (3.1±1.5 cm) in (PR) group compared to that in (NC) group (7.6±4.6 cm) a3er treatment (p<0.05).Conclusions: We concluded that there was a relation between the99mTc-MIBI uptake in NSCLC and the response to chemotherapy, the higher uptake of 99mTc-MIBI and relatively higher early and late T/NL ratios were more likely to respond to chemotherapy. The use of 99mTc-MIBI to preselect chemotherapy responders would result in significant cost savings for the health care system.