Significance Resolution of inflammation is an active process that restores tissue homeostasis and prevents the development of chronic inflammatory diseases. The mechanisms that regulate resolution of inflammation are only partially understood. Here, we showed that activation of the vagus nerve accelerated resolution of inflammation. Electrical stimulation of the vagus nerve in vivo increased levels of select specialized proresolving mediators in inflammation. Experiments in genetic mouse models revealed that the mechanism involved 12/15-lipoxgenase (Alox15), a key enzyme for biosynthesis of the identified mediators, and required the α7-nicotinic acetylcholine receptor subunit. The findings indicate that electrical signals in the vagus nerve activate a cholinergic signal promoting Alox15-dependent lipid mediator biosynthesis and accelerating resolution of inflammation, providing additional insights into neural regulation of inflammation.