•  A central neural apnoea in the absence of hypoxia elicits a form of respiratory plasticity known as inactivity‐induced phrenic motor facilitation (iPMF), a rebound increase in phrenic burst amplitude when central respiratory neural activity is restored. •  iPMF requires spinal atypical protein kinase C (aPKC) activity in spinal segments encompassing the phrenic motor nucleus. •  Here, we report novel findings that tumour necrosis factor‐α (TNFα) signalling in or near the phrenic motor pool is necessary and sufficient for iPMF as: (1) spinal TNFα inhibition inhibits iPMF; and (2) spinal TNFα elicits long‐lasting increases in phrenic burst amplitude via an aPKC‐dependent mechanism. •  These data are consistent with the hypothesis that local mechanisms operating within or near the phrenic motor pool sense and respond to reduced respiratory neural activity, and suggest that TNFα‐induced activation of aPKC near phrenic motor neurons forms part of the core cellular pathway giving rise to iPMF. Abstract  A prolonged reduction in central neural respiratory activity elicits a form of plasticity known as inactivity‐induced phrenic motor facilitation (iPMF), a ‘rebound’ increase in phrenic burst amplitude apparent once respiratory neural activity is restored. iPMF requires atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize an early transient increase in phrenic burst amplitude and to form long‐lasting iPMF following reduced respiratory neural activity. Upstream signal(s) leading to spinal aPKC activation are unknown. We tested the hypothesis that spinal tumour necrosis factor‐α (TNFα) is necessary for iPMF via an aPKC‐dependent mechanism. Anaesthetized, ventilated rats were exposed to a 30 min neural apnoea; upon resumption of respiratory neural activity, a prolonged increase in phrenic burst amplitude (42 ± 9% baseline; P < 0.05) was apparent, indicating long‐lasting iPMF. Pretreatment with recombinant human soluble TNF receptor 1 (sTNFR1) in the intrathecal space at the level of the phrenic motor nucleus prior to neural apnoea blocked long‐lasting iPMF (2 ± 8% baseline; P > 0.05). Intrathecal TNFα without neural apnoea was sufficient to elicit long‐lasting phrenic motor facilitation (pMF; 62 ± 7% baseline; P < 0.05). Similar to iPMF, TNFα‐induced pMF required spinal aPKC activity, as intrathecal delivery of a ζ‐pseudosubstrate inhibitory peptide (PKCζ‐PS) 35 min following intrathecal TNFα arrested TNFα‐induced pMF (28 ± 8% baseline; P < 0.05). These data demonstrate that: (1) spinal TNFα is necessary for iPMF; and (2) spinal TNFα is sufficient to elicit pMF via a similar aPKC‐dependent mechanism. These data are consistent with the hypothesis that reduced respiratory neural activity elicits iPMF via a TNFα‐dependent increase in spinal aPKC activity.