Here we report that macrophages in the rat superior cervical ganglia (SCG) respond differently to pre- and postganglionic axotomy. Postganglionic axotomy results in a rapid activation of resident macrophages, as measured by inducible nitric oxide synthase (iNOS) immunoreactivity, and a massive invasion by macrophages. Following preganglionic lesion there was no such rapid activation and the macrophage invasion was of much lower magnitude. A subpopulation of the macrophages also expressed haem oxygenase-1 (HO-1). The results are compatible with a model in which macrophages or their products, including nitric oxide (NO) and carbon monoxide (CO) could be important for induction of early changes in the nerve cell body, like an altered neuropeptide synthesis, which has been shown to accompany the regenerative response in peripheral ganglia.