Strengthening of the quadriceps femoris muscle (QFM) is of great importance in the treatment of the patients with knee osteoarthritis (OA). In this study, we aimed to investigate and compare the effects of neuromuscular electrical stimulation (NMES) and isometric exercises (IsE) on QFM by 99mTc-sestamibi scintigraphy which is a new skeletal muscle perfusion agent. Twenty female patients aged between 41-62 years, diagnosed as having knee OA according to American College of Rheumatology (ACR) criteria were included in the study. Radiograms of the knees were taken, thigh girth and Lequesne index values were obtained in all cases before and after the training activities. After randomization, one QFM of each case was subjected to the procedure of NMES for 23 minutes daily by Compex device which is a computed electrostimulator, whereas the other was applied IsE for 9.5 minutes daily, five times a week for three weeks’ period. 99mTc-sestamibi scintigraphic evaluations were performed 3 days before and after the training programmes and thigh uptake ratios were calculated from the images. Significant increases in thigh uptake ratios were determined in both groups, however this increase did not reach significant difference between the groups. Significant increases were also found in thigh girth values for both groups whereas the mean value of increase was much more apparent in NMES group. The increases in uptake ratios and thigh girth improvement values were significant in cases of stage I when compared with advanced radiological stages. Clinical improvement in Lequesne indices were found to be concordant with scintigraphic increases in all cases. Finally, it was concluded that NMES and IsE training activities seemed to increase muscle perfusion as shown by 99mTc-sestamibi scintigraphy. Muscle strengthening methods were more effective in cases with early radiological stages knee OA. 99mTc-sestamibi scintigraphy can be considered in evaluation of effects of muscle rehabilitation methods on muscle perfusion and mitochondrial fraction as a new, cheap and non-invasive method.