People with Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations of the MECP2 gene, show breathing abnormalities that are attributable to the high incidence of sudden death. To understand the underlying mechanisms for the breathing disorders, direct in vivo recordings from brainstem neurons with respiratory rhythm are needed, which is a challenge in mouse RTT models. The newly available rat model may allow such a study. Therefore, we performed electrophysiological recording from individual neurons of the medullary ventral respiratory group (VRG) in decerebrate Mecp2‐null and wild‐type (WT) rats. In both groups of rats, neurons with expiratory rhythm were recorded from the rostral and caudal VRG, and cells with inspiratory rhythm were found in between. Firing frequency of the inspiratory neurons was significantly lower in null rats than in WT rats, while expiratory neurons in both rostral and caudal VRG did not show such a difference. Firing durations of both expiratory and inspiratory neurons were elongated in null rats compared with the WT. The ratio of inspiratory to expiratory firing duration (Ti/Te) was lower in null rats. A large number of cells showed E‐I phase‐spanning in null rats. The null rats had a frequent breathing pattern of apneusis followed by apnea, during which inspiratory neurons showed increased firing frequency and caudal expiratory neurons showed decreased firing frequency, whereas no significant change was observed in rostral expiratory neurons. Although this breathing pattern of apneusis followed by apnea was also seen in WT rats, the firing frequency of either respiratory neurons did not seem to change. These findings suggest that Mecp2 disruption appears to cause a large scale of changes in firing activity and pattern of medullary respiratory neurons consistent with the broad range of breathing abnormalities seen in people with RTT and animal models.Support or Funding InformationThis work was supported by NIH grant R01‐NS‐073875 and International Rett Syndrome Foundation.