To study whether neuronal regeneration occurs after laserinduced interstitial thermotherapy (LITT) of the brain, we examined lesions and their margins in adult Lewis rats with histological and immunohistochemical methods. We used the Bodian stain and antibodies against β‐amyloid precursor protein (APP), which has been associated with trophic effects in neural regeneration and against heat‐shock protein 72 (HSP 72) and neurofilament 68 (NF 68). The glial reaction was monitored with antibodies against glial fibrillary acidic protein (GFAP) and apolipoprotein E (Apo E). β‐Amyloid precursor protein showed a distinct temporal profile in areas of lesion margins thought to be associated with neurite sprouting and regeneration. Axonal accumulation of APP started 1 h after LITT and reached a maximum after 3 days. Heat‐shock protein 72 was weakly positive in isolated marginal neurons in the early postoperative period. Subsequent to GFAP expression, Apo E immunoreactivity was detected in reactive astrocytes but not in profiles thought to be axonal sprouts. The results showed that margins of LITT‐induced lesions contain profiles which resemble sprouting neurites and are similar to those found after injury or ischemia but with differences in the time course of reactive proteins.