N-methyl-D-aspartate receptor (NMDA) antagonists, such as phencyclidine (PCP), sub-chronically (sc) administrated to rodents, can lead to robust and prolonged deficits in cognitive functions and mimic neurobiological deficits found in schizophrenia. Glycogen synthase kinase-3β (GSK-3β) inhibition has been identified as an important treatment for cognitive impairment in diverse neuropsychiatric diseases. However, whether GSK-3β inhibition rescues the cognitive deficits in a model of NMDA receptor hypofunction is unknown. This study examined the acute and sub-chronic effects of GSK-3β inhibition on cognitive deficits in the scPCP rat model. Female Lister Hooded rats (n=60) were dosed with scVehicle or scPCP (bidaily, 7 days, i.p.). After a washout, rats were treated with the GSK-3β inhibitor SB216763 at 2 and 5 mg/kg (daily, 7 days, i.p.). Cognition was assessed using the novel object recognition (NOR) test, analogous to human visual recognition memory, a cognitive domain impaired in schizophrenia. In group one, NOR testing was conducted after 1 and 7 days of treatment. In group two, NOR testing was conducted on day 7 and after a 7-day washout of SB216763. Both doses of SB216763 attenuated the scPCP-induced NOR deficit when given acutely or sub-chronically. The positive treatment effects persisted after a 7-day washout. These findings demonstrate the efficacy of GSK-3β inhibition to rescue cognitive impairments induced by NMDA receptor hypofunction. Moreover, it highlights a potential role for GSK-3β inhibitors in the treatment of cognitive impairment associated with schizophrenia. Post-mortem analyses to understand the underlying mechanisms of these improvements are ongoing.