Macrophagic myofasciitis (MMF) is a specific histopathologic lesion involved in the persistence for years of aluminum hydroxide [Al(OH)3] at the site of previous intramuscular (i.m.) injection. In order to study mechanisms involved persistence of MMF lesions, we set up an experimental model of MMF-lesion in Sprague–Dawley and Lewis rat, by i.m. injections of 10 μL of an Al(OH)3-adjuvanted vaccine. An evaluation carried out over a 12-month period disclosed significant shrinkage of MMF lesions with time. A radioisotopic study did not show significant aluminium uptake by Al(OH)3-loaded macrophages. A morphometric approach showed that Lewis rats with Th1-biased immunity had significantly smaller lesions than Sprague–Dawley rats with balanced Th1/Th2 immunity. Concluding, our results indicate that genetic determinatives of cytotoxic T-cell responses could interfere with the clearance process and condition the persistence of vaccine-induced MMF-lesions.