We have investigated the possibility of determining changes in the volume fraction of microstructure scatterers in the superficial tissue layers by using diffuse reflectance spectroscopy. To that extent we have built a two-layer optical phantom by using microparticles with various sizes in order to simulate the scattering properties of tissue microstructures. Reflectance spectral measurements were performed on a number of optical phantoms having different volume fractions of various microparticle sizes. An analytical model was developed using light-transport theory and fractal modeling approaches and was then fitted to the measured reflectance to calculate the volume fractions of the microparticles in phantoms. The results showed that we could measure changes in both the total volume fraction of the microparticles and in the overall size distribution of the microparticles with good accuracy \left(>80\%\right) . These results suggest the potential of using this method for measuring the volume fraction changes of tissue microstructure scatterers and applications in the detection of cancerous related morphological and structural changes.