Precise assessment of spinal cord cystic lesions is crucial to formulate effective therapeutic strategies, yet histological assessment of the lesion remains the primary method despite numerous studies showing inconsistent results regarding estimation of lesion size via histology. On the other hand, despite numerous advances in micro-computed tomography (micro-CT) imaging and analysis that have allowed precise measurements of lesion size, there is not enough published data on its application to estimate intraspinal lesion size in laboratory animal models. This work attempts to show that micro-CT can be valuable for spinal cord injury research by demonstrating accurate estimation of syrinx size and compares between micro-CT and traditional histological analysis. We used a post-traumatic syringomyelia rat model to compare micro-CT analysis to conventional histological analysis. The study showed that micro-CT can detect lesions within the spinal cord very similar to histology. Importantly, micro-CT appears to provide more accurate estimates of the lesions with more measures (e.g., surface area), can detect compounds within the cord, and can be done with the tissue of interest (spinal cord) intact. In summary, the experimental work presented here provides one of the first investigations of the use of micro-CT for estimating the size of intraparenchymal cysts and detecting materials within the spinal cord. All animal procedures were approved by the University of Akron Institutional Animal Care and Use Committee (IACUC) (protocol # LRE 16-05-09 approved on May 14, 2016).