We wanted to find out if any of three different types of manipulations: a piece of muscle or nerve put parallel to a nerve; an epineurial window made, or sutures inserted into a nerve, or both; or pieces of nerve sutured to an epineurial window end-to-side to the musculocutaneous or sciatic nerve, resulted in activation of activating transcription factor 3 (ATF3) in neurons and in non-neuronal cells. ATF3, a marker of cell activation, was investigated by immunocytochemistry one week after manipulation. A piece of nerve or muscle parallel to a nerve did not induce ATF3 locally in the nerve and induced ATF3 only rarely in neurons. In contrast, an epineurial window or insertion of sutures, or both, with or without attachment of a piece of nerve placed end-to-side, induced robust ATF3 expression. We conclude that an injury to a peripheral nerve trunk associated with end-to-side nerve repair, activates neurons and non-neuronal cells and may contribute to sprouting of axons into the nerve attached end-to-side.