We experimentally investigate the influences of irradiation and annealing process on the microstructure properties of optical fiber cladding material. The electron spin resonance (ESR) results reveal that the defect concentration significantly decreases after silica fiber cladding material is irradiated by ã-rays with a successive thermal annealing process. Raman analysis show the irradiated microstructure of cladding material change little, after irradiation, which indicates that the three- and four-membered rings (3-MRs and 4-MRs) structures are stable. However, after thermal annealing process, Raman spectrum shows that 3-MRs and 4-MRs are reduced obviously, which means that the ring structures are broken after thermal annealing and new stable structures are formed. X-ray diffraction (XRD) also shows that slight crystallization occurs when the annealing temperature is equal to 1000°C. We conclude that Si-O bonds around 3-MRs and 4-MRs are easier to fracture, where color centers are formed. We also show the microstructure models explained by the theory of quantum chemistry.