The aim of this study was to determine whether contrast-enhanced micro-computed tomography can be used for non-invasive imaging of the early-stage changes in the vasculature of tumours that have been treated with photodynamic therapy (PDT). The subjects used were C3H mice with an RIF-1 tumour implanted subcutaneously and allowed to grow for 3 weeks prior to treatment. The experimental groups were PDT-treated (150 J/cm² and 50 J/cm²) and control (150 J/cm² light-only and untreated). The laser light exposure was performed at 15 - 30 minutes after the administration of the photosensitizer (BPD-MA). The contrast-enhanced micro-computed tomography imaging procedure consisted of eight-second scans taking place before treatment and up to 24 hours after treatment. The 150 J/cm² PDT group showed a significant increase in the ratio of blood volume to tumour volume at 2, 8 and 24 hours after treatment when compared to pre-treatment measurements (p < 0.01). The observed increase in the blood volume to tumour volume at the later time points corresponds to a decrease in epithelial coverage on immunohistochemical stained (CD31) slides for the 150 J/cm² PDT group at 24 hours after treatment. This preliminary study indicates that micro-CT can detect compromised vasculature in tumours treated with high-fluence photodynamic therapy as early as 2 hours post treatment.