During the critical period, cortical networks employ a number of homeostatic feedback mechanisms in order to balance feedforward modifications to synaptic strength. Reducing visual drive during the critical period with intraocular injection of TTX or brief dark-rearing (DR) leads to a scaling up of AMPA mEPSC amplitudes [Desai et al, Nat Neurosci, 8:783; Goel & Lee, J Neurosci, 27(25):6692], which may help compensate for deprivation-induced response attenuation within the cortical network. Recent in vitro work has shown that glial release of the cytokine tumor necrosis factor-alpha (TNFa) is necessary for scaling up mEPSC amplitudes at hippocampal synapses in response to activity blockade [Stellwagen & Malenka, Nature, 440:1054]. We asked whether this glial-derived factor is important for activity-dependent scaling of visual responses in vivo, measured by shifts in the balance of feedback and feedforward mechanisms induced by visual deprivation. We find that TNFa immunoreactivity is indeed present in both glia and a population of neurons throughout V1. In vivo intrinsic signal optical imaging was performed on wildtype (WT) and TNFa-/- mice at the peak of the critical period (age P28 - P29) to measure visual response strengths after 4 - 5 days of DR or binocular lid suture (BLS). We detect a significant enhancement (p < 0.05) of binocular responses after 4 - 5 days DR, consistent with an early feedback response that offsets decreases in visual drive. In contrast, we observe a significant response decrease (p < 0.05) in mice lacking TNFa, consistent with feedforward depression that is not countered by feedback enhancement. Further, we also observe a modest response attenuation in TNFa-/- mice after BLS that is not seen in WT mice. Thus TNFa is critical for activity-dependent increases in visual responses, which are necessary to prevent or counter response depression during sensory deprivation. Other aspects of visual circuitry are likely unchanged in these mice, as maps of retinotopy and ocular dominance were indistinguishable from WT. Interestingly, baseline visual responses were on average 38% greater in nondeprived TNFa-/- mice than their WT counterparts, suggesting TNFa may also be important developmentally for establishing the set point for firing rates. These data indicate a central role for TNFa in maintaining a balanced level of excitation in vivo.