Background: Inferior oblique muscle overaction is a common disorder that has a correlation with the anatomical changes of the muscle itself. The changes differ according to the grade of the overaction. Objective: To correlate between the histopathological alternations of the inferior oblique muscle and the different degrees of clinical overaction. Patients and methods: Ten biopsies from inferior oblique muscles were taken during the surgery of strabismus after determining the clinical degree of the overaction. One muscle biopsy was taken during enucleation surgery and considered as a control. All biopsies were examined by light and transmission electron microscopes. Results: By light microscopy, grade II and grade III inferior oblique overaction showed many histopathological findings as muscle fibers degeneration, variable size of muscle fibers, nerve bundles hypertrophy and fibro-fatty infiltrations. Grade III inferior oblique overaction showed fibrosis of perimysium and endomysium, mononuclear infiltration and fatty infiltration. By transmission electron microscopy the muscle fibers showed increased mitochondrial number and mitochondrial variability in shape and size, also showed increased vacuoles and fat droplets. Conclusion: Histopathological alternations in the inferior oblique muscle correlate to the clinical grades of the muscle overaction.